PEG修饰人犬嵌合尿酸酶结构功能研究及临床前药理学评价
|
摘要
尿酸酶[EC 1.7.3.3]是嘌呤代谢过程中的一种酶,它可将尿酸水解为更易溶于水的尿囊素。人类由于基因突变而缺乏活性尿酸酶,这导致人类以尿酸作为嘌呤代谢的终产物。当人血液中尿酸浓度高于其溶解度(高尿酸血症)时可引起尿酸性肾病和痛风性关节炎。天然(UricozymeTM)和重组(ElitekTM)的Aspergillus flavus来源尿酸酶已被用于急性高尿酸血症的治疗,但是这种微生物来源尿酸酶的强免疫原性和短半衰期限制了他们对慢性高尿酸血症及痛风的治疗。PEG修饰可降低尿酸酶的免疫原性并延长其体内半衰期,因此人们从1981年即已开展PEG修饰尿酸酶的临床前研究,但是到目前为止只有一个PEG修饰尿酸酶类药物上市(KrystexxaTM)。然而,Krystexxa的临床前研究表明92%的病人产生了特异性抗体而且57%的病人多次注射Krystexxa后出现了体内降低尿酸效果减弱的现象,此外这个由10kDa mPEG修饰的类似猪源尿酸酶只能用于静脉推注。据我们所知,到目前为止还没有免疫原性更低的注射途径更方便的PEG修饰尿酸酶药物上市。
本课题首先以犬源尿酸酶为基础筛选得到了同源性、活性、四聚体稳定性和回收率更高的人犬嵌合尿酸酶；利用特制的5 kDa mPEG-SPA修饰剂对高纯度重组四聚体人犬嵌合尿酸酶进行饱和修饰,并对修饰后人犬嵌合尿酸酶蛋白的临床前药理学性质和安全性进行了初步评价。
第一部分：人犬嵌合尿酸酶的构建、筛选和结构功能研究
鉴于犬源尿酸酶较高的催化活性及其与推测出的人源尿酸酶的高同源性,首先在大肠杆菌中重组表达制备了犬源尿酸酶。以此为基础构建了5个人犬嵌合尿酸酶,并对其基本性质进行了研究。最终筛选到的人犬嵌合尿酸酶与初始犬源尿酸酶相比,活性和稳定性均有显著提高。以最优的人犬嵌合尿酸酶为基础进行了同源建模并对与活性和稳定性相关的关键氨基酸区域进行了研究：哺乳动物尿酸酶C末端的291-304位氨基酸对于维持蛋白的活性和稳定性至关重要,而位于H4区域下半部分和S7区域上半部分的245-253位氨基酸与四聚体尿酸酶蛋白的回收率和稳定性有关。同时,利用分子对接和分子动力学模拟等方法确认了人犬嵌合尿酸酶的活性中心,扩宽了一个新颖的氧气结合位点的氨基酸构成,并首次确认了活性中心附近的高度保守氨基酸的功能。利用质量肽图确认了人犬嵌合尿酸酶的氨基酸序列,并结合SE-HPLC和亲和层析的方法首次确认了尿酸酶家族蛋白中广泛存在的与二硫键无关的活性共价二聚体的构成形式。利用封闭游离半胱氨酸、胰蛋白酶酶切和液质联用的方法确认了哺乳动物尿酸酶中序列高度保守的4个半胱氨酸残基的构成形式并对其功能进行了分析。
第二部分：开发免疫原性足够低的PEG修饰哺乳动物尿酸酶
首先成功纯化并鉴定了四聚体和多聚体尿酸酶蛋白。在接下来的PEG修饰中,利用阴离子交换层析的方法除掉了PEG修饰剂中的PEG Diol,并将四聚体尿酸酶和多聚体尿酸酶分别与除掉PEG Diol前后的5kDa mPEG-SPA修饰剂进行反应,制备了三种不同形式的PEG修饰尿酸酶。尿酸酶多聚体可以降低PEG修饰后蛋白的酶活保留率,除去该多聚体后可消除这种影响,且四聚体尿酸酶修饰后酶活保留率可大于85%。动态光散射系统和透射电镜技术首次成功用于分析不同PEG修饰蛋白的大小分布。接下来我们研究了PEG修饰蛋白多聚体及PEG Diol引起的交联多聚体对修饰后尿酸酶蛋白体内药代动力学和免疫原性的影响。大鼠在多次注射PEG修饰多聚体后出现了已经在PEG修饰脂质体中被确认的血液清除加快(ABC)现象。介导这种清除加快现象的不是中和抗体而是针对mPEG的IgM抗体,而且我们认为PEG修饰物的大小是诱发此类现象的首要因素。除去尿酸酶多聚体和PEG修饰剂中的PEG Diol杂质后,可成功避免此类现象的出现。
第三部分：5 kDa mPEG修饰人犬嵌合尿酸酶的临床前药理和安全性评价
首先构建了三个不同的动物模型分别用来评价5 kDa mPEG修饰人犬嵌合尿酸酶的降低血液尿酸作用、对尿酸性肾病的预防作用和对痛风性关节炎的治疗作用。在大鼠和食蟹猴体内静脉注射rnPEG-UHC后消除半衰期分别为34.9小时和134.3小时。两种动物体内皮下注射的生物利用度都高于60%,这表明皮下注射可以作为临床治疗时一个候选的注射途径。大鼠28天毒性研究表明,在临床观察、血液学和血液生化方面均未发现与药物相关的毒性作用。唯一的与给药相关的器官组织形态学改变是在1只中剂量大鼠(12.5%)和两只高剂量大鼠(25%)中发现了脾脏巨噬细胞空泡样变化,这种改变可能是由于针对]mPEG的IgM抗体介导并引发了脾脏单核巨噬细胞对mPEG-UHC蛋白的吞噬作用,但是这种改变并未带来任何病理性改变和功能性损伤。
本研究不仅提供了一个非常有价值的痛风治疗候选药物,而且对整个尿酸酶家族的结构和催化机理研究、由PEG修饰蛋白和纳米颗粒引起的血液清除加快现象研究、PEG修饰大分子蛋白的体内代谢和安全性研究等方面均有很好的参考价值。
Uricase [EC 1.7.3.3] is an enzyme involved in the purine degradation pathway and catalyzes the hydrolysis of uric acid to the more water-soluble allantoin. Human beings lack active uricase because of gene mutations, leading to uric acid as the end product of purine metabolism and resulting in the development of urate nephropathy and gouty arthritis when the concentration of uric acid reaches its solubility limit in blood (hyperuricemia). Both the natural (UricozymeTM) and recombinant (ElitekTM) Aspergillus Flavus uricases had been used therapeutically in patients with acute hyperuricemia but their high immunogenicity and short half-life has limited their long-term use for treating chronic hyperuricemia and associated diseases (gout). PEGylated uricase, with low immunogenicity and a long circulation half-life has been under preclinical investigation since 1981, but there has been only one commercial PEGylated uricase treatment (KrystexxaTM) used in clinical therapy. However,92% of patients developed antibodies and 57% of patients showed decreased urate-lowing efficacy after repeated administrations in the clinical trials of Krystexxa. Moreover, the only commercially marketed 10 kDa mPEG modified porcine-like uricase can only be used for intravenous infusion. As far as we know, to date no form of uricase or PEGylated uricase has been developed that has sufficiently reduced immunogenicity for safe and reliable use in chronic therapy.
In this thesis, we first screened and finalized canine-human chimeric uricase with high enzymatic activity, recovery and stability than the original wild-type canine uricase. Homogeneous recombinant tetrameric chimeric uricase was successfully purified and then modified to saturation with a tailored 5 kDa mPEG-SPA. The preclinical pharmacology and safety properties of the PEGylated canine-human chimeric uricase was investigated in vivo.
Section one:Construction, screening and structure-based characterization of canine-human chimeric uricase
Canine uricase was first selected for recombinant expression and production in E.coli, due to its high catalytic activity and identity with deduced human uricase. Five chimeric uricase uricases based on the wild-type canine uricase were constructed and characterized. Both the activity and stability of the finalized uricases were improved compared to the original uricase. Homology modeling was used to analyze the enhancements:the C-terminus of mammalian uricase (residues 291-304) is important for maintaining the activity and stability of the protein, whereas the lower domain of H4 and the upper part of S7 (residues 245-253) are associated with the recovery and stability of tetrameric uricase. In addition, substrate docking and molecular dynamics simulations were performed to confirm the active center of the chimeric uricase uricase. A novel oxygen binding architecture was clarified and the function of several highly conserved residues was investigated for the first time. The amino acid sequence was confirmed by using peptide mapping. A novel active non-disulfide covalent cross-linked dimer, which was widely existed in uricase family, was first structurally confirmed by using peptide mapping, size exclusion HPLC and affinity chromatography. The statues and function of the highly conserved cysteine residues in mammalian uricase were investigated by blocking free cysteine, then digested with trypsin and analyzed using HPLC-MS methods.
Section two:Development of novel PEGylated mammalian uricase with sufficiently reducing of immunogenicity
Tetrameric and large aggregated uricase proteins were successfully purified and characterized. In the subsequent pegylation process, anion-exchange chromatography was employed to remove the PEG Diol from PEG reagents. Uricase with or without aggregates was modified to saturation with purified or unfractionated 5 kDa mPEG-SPA, respectively, resulting in three kinds of PEGylated uricases. Large uricase aggregates could affect enzymatic retention but the impact could be resolved after removing the aggregates and the enzymatic retention of PEGylated tetrameric uricase was higher than 85%. Dynamic light scattering and transmission electron microscope were first employed to analyze the size distribution of different PEGylated proteins. The impact of unmodified uricase aggregates and cross-linked uricase congregates induced by PEG Diol on pharmacokinetics and immunogenicity were studied in vivo. The accelerated blood clearance phenomenon previously identified in PEGylated liposomes, also appeared in rats injected with PEGylated uricase aggregates. Anti-PEG IgM antibodies rather than neutralizing antibodies were found to mediate the accelerated blood clearance. Moreover, we confirmed for the first time that the size of conjugates is of primary important in triggering such phenomena. After removal of uricase aggregates and PEG Diol, accelerated blood clearance could be successfully avoided. Section Three:Preclinical pharmacology and safety evaluation of 5 kDa mPEG modified canine-human chimeric uricase
Three different animal models were first set up to evaluate the urate-lowering efficacy, preventive effect on urate nephropathy and therapeutic effect on gouty arthritis, respectively. The pharmacokinetic properties and the bioavailability of subcutaneous injection of mPEG-UHC were evaluated in rodents and non-human privates. The elimination half-life of intravenous injection of mPEG-UHC in rats and monkeys were 34.9h and 134.3h. The systemic bioavailability of mPEG-UHC after subcutaneous administration in the above two species is higher than 60%, indicating that subcutaneous injection may be regarded as a candidate administration route. According to 28-day toxicity studies, there were no test article-related effects on clinical observations, hematology and blood biochemistry test. The only treatment-related histopathological changes were the vacuolation of splenic macrophages in one middle-dose (12.5%) and two high-dose (25%) rats, which may be caused by the inducing of anti-PEG IgM antibody and triggering of the uptake of mPEG-UHC by the mononuclear phagocyte system in spleen, but such change did not bring any pathology changes and functional lesions.
This findings not only provide a worthy drug candidate for treating gout, but also represent a valuable resource for understanding the structure and catalytic mechanism of the whole uricase family, the mechanism of accelerated blood clearance triggered by PEGylated proteins and nanoparticles, the elimination mechanism and safety of large PEGylated proteins.
本课题首先以犬源尿酸酶为基础筛选得到了同源性、活性、四聚体稳定性和回收率更高的人犬嵌合尿酸酶；利用特制的5 kDa mPEG-SPA修饰剂对高纯度重组四聚体人犬嵌合尿酸酶进行饱和修饰,并对修饰后人犬嵌合尿酸酶蛋白的临床前药理学性质和安全性进行了初步评价。
第一部分：人犬嵌合尿酸酶的构建、筛选和结构功能研究
鉴于犬源尿酸酶较高的催化活性及其与推测出的人源尿酸酶的高同源性,首先在大肠杆菌中重组表达制备了犬源尿酸酶。以此为基础构建了5个人犬嵌合尿酸酶,并对其基本性质进行了研究。最终筛选到的人犬嵌合尿酸酶与初始犬源尿酸酶相比,活性和稳定性均有显著提高。以最优的人犬嵌合尿酸酶为基础进行了同源建模并对与活性和稳定性相关的关键氨基酸区域进行了研究：哺乳动物尿酸酶C末端的291-304位氨基酸对于维持蛋白的活性和稳定性至关重要,而位于H4区域下半部分和S7区域上半部分的245-253位氨基酸与四聚体尿酸酶蛋白的回收率和稳定性有关。同时,利用分子对接和分子动力学模拟等方法确认了人犬嵌合尿酸酶的活性中心,扩宽了一个新颖的氧气结合位点的氨基酸构成,并首次确认了活性中心附近的高度保守氨基酸的功能。利用质量肽图确认了人犬嵌合尿酸酶的氨基酸序列,并结合SE-HPLC和亲和层析的方法首次确认了尿酸酶家族蛋白中广泛存在的与二硫键无关的活性共价二聚体的构成形式。利用封闭游离半胱氨酸、胰蛋白酶酶切和液质联用的方法确认了哺乳动物尿酸酶中序列高度保守的4个半胱氨酸残基的构成形式并对其功能进行了分析。
第二部分：开发免疫原性足够低的PEG修饰哺乳动物尿酸酶
首先成功纯化并鉴定了四聚体和多聚体尿酸酶蛋白。在接下来的PEG修饰中,利用阴离子交换层析的方法除掉了PEG修饰剂中的PEG Diol,并将四聚体尿酸酶和多聚体尿酸酶分别与除掉PEG Diol前后的5kDa mPEG-SPA修饰剂进行反应,制备了三种不同形式的PEG修饰尿酸酶。尿酸酶多聚体可以降低PEG修饰后蛋白的酶活保留率,除去该多聚体后可消除这种影响,且四聚体尿酸酶修饰后酶活保留率可大于85%。动态光散射系统和透射电镜技术首次成功用于分析不同PEG修饰蛋白的大小分布。接下来我们研究了PEG修饰蛋白多聚体及PEG Diol引起的交联多聚体对修饰后尿酸酶蛋白体内药代动力学和免疫原性的影响。大鼠在多次注射PEG修饰多聚体后出现了已经在PEG修饰脂质体中被确认的血液清除加快(ABC)现象。介导这种清除加快现象的不是中和抗体而是针对mPEG的IgM抗体,而且我们认为PEG修饰物的大小是诱发此类现象的首要因素。除去尿酸酶多聚体和PEG修饰剂中的PEG Diol杂质后,可成功避免此类现象的出现。
第三部分：5 kDa mPEG修饰人犬嵌合尿酸酶的临床前药理和安全性评价
首先构建了三个不同的动物模型分别用来评价5 kDa mPEG修饰人犬嵌合尿酸酶的降低血液尿酸作用、对尿酸性肾病的预防作用和对痛风性关节炎的治疗作用。在大鼠和食蟹猴体内静脉注射rnPEG-UHC后消除半衰期分别为34.9小时和134.3小时。两种动物体内皮下注射的生物利用度都高于60%,这表明皮下注射可以作为临床治疗时一个候选的注射途径。大鼠28天毒性研究表明,在临床观察、血液学和血液生化方面均未发现与药物相关的毒性作用。唯一的与给药相关的器官组织形态学改变是在1只中剂量大鼠(12.5%)和两只高剂量大鼠(25%)中发现了脾脏巨噬细胞空泡样变化,这种改变可能是由于针对]mPEG的IgM抗体介导并引发了脾脏单核巨噬细胞对mPEG-UHC蛋白的吞噬作用,但是这种改变并未带来任何病理性改变和功能性损伤。
本研究不仅提供了一个非常有价值的痛风治疗候选药物,而且对整个尿酸酶家族的结构和催化机理研究、由PEG修饰蛋白和纳米颗粒引起的血液清除加快现象研究、PEG修饰大分子蛋白的体内代谢和安全性研究等方面均有很好的参考价值。
Uricase [EC 1.7.3.3] is an enzyme involved in the purine degradation pathway and catalyzes the hydrolysis of uric acid to the more water-soluble allantoin. Human beings lack active uricase because of gene mutations, leading to uric acid as the end product of purine metabolism and resulting in the development of urate nephropathy and gouty arthritis when the concentration of uric acid reaches its solubility limit in blood (hyperuricemia). Both the natural (UricozymeTM) and recombinant (ElitekTM) Aspergillus Flavus uricases had been used therapeutically in patients with acute hyperuricemia but their high immunogenicity and short half-life has limited their long-term use for treating chronic hyperuricemia and associated diseases (gout). PEGylated uricase, with low immunogenicity and a long circulation half-life has been under preclinical investigation since 1981, but there has been only one commercial PEGylated uricase treatment (KrystexxaTM) used in clinical therapy. However,92% of patients developed antibodies and 57% of patients showed decreased urate-lowing efficacy after repeated administrations in the clinical trials of Krystexxa. Moreover, the only commercially marketed 10 kDa mPEG modified porcine-like uricase can only be used for intravenous infusion. As far as we know, to date no form of uricase or PEGylated uricase has been developed that has sufficiently reduced immunogenicity for safe and reliable use in chronic therapy.
In this thesis, we first screened and finalized canine-human chimeric uricase with high enzymatic activity, recovery and stability than the original wild-type canine uricase. Homogeneous recombinant tetrameric chimeric uricase was successfully purified and then modified to saturation with a tailored 5 kDa mPEG-SPA. The preclinical pharmacology and safety properties of the PEGylated canine-human chimeric uricase was investigated in vivo.
Section one:Construction, screening and structure-based characterization of canine-human chimeric uricase
Canine uricase was first selected for recombinant expression and production in E.coli, due to its high catalytic activity and identity with deduced human uricase. Five chimeric uricase uricases based on the wild-type canine uricase were constructed and characterized. Both the activity and stability of the finalized uricases were improved compared to the original uricase. Homology modeling was used to analyze the enhancements:the C-terminus of mammalian uricase (residues 291-304) is important for maintaining the activity and stability of the protein, whereas the lower domain of H4 and the upper part of S7 (residues 245-253) are associated with the recovery and stability of tetrameric uricase. In addition, substrate docking and molecular dynamics simulations were performed to confirm the active center of the chimeric uricase uricase. A novel oxygen binding architecture was clarified and the function of several highly conserved residues was investigated for the first time. The amino acid sequence was confirmed by using peptide mapping. A novel active non-disulfide covalent cross-linked dimer, which was widely existed in uricase family, was first structurally confirmed by using peptide mapping, size exclusion HPLC and affinity chromatography. The statues and function of the highly conserved cysteine residues in mammalian uricase were investigated by blocking free cysteine, then digested with trypsin and analyzed using HPLC-MS methods.
Section two:Development of novel PEGylated mammalian uricase with sufficiently reducing of immunogenicity
Tetrameric and large aggregated uricase proteins were successfully purified and characterized. In the subsequent pegylation process, anion-exchange chromatography was employed to remove the PEG Diol from PEG reagents. Uricase with or without aggregates was modified to saturation with purified or unfractionated 5 kDa mPEG-SPA, respectively, resulting in three kinds of PEGylated uricases. Large uricase aggregates could affect enzymatic retention but the impact could be resolved after removing the aggregates and the enzymatic retention of PEGylated tetrameric uricase was higher than 85%. Dynamic light scattering and transmission electron microscope were first employed to analyze the size distribution of different PEGylated proteins. The impact of unmodified uricase aggregates and cross-linked uricase congregates induced by PEG Diol on pharmacokinetics and immunogenicity were studied in vivo. The accelerated blood clearance phenomenon previously identified in PEGylated liposomes, also appeared in rats injected with PEGylated uricase aggregates. Anti-PEG IgM antibodies rather than neutralizing antibodies were found to mediate the accelerated blood clearance. Moreover, we confirmed for the first time that the size of conjugates is of primary important in triggering such phenomena. After removal of uricase aggregates and PEG Diol, accelerated blood clearance could be successfully avoided. Section Three:Preclinical pharmacology and safety evaluation of 5 kDa mPEG modified canine-human chimeric uricase
Three different animal models were first set up to evaluate the urate-lowering efficacy, preventive effect on urate nephropathy and therapeutic effect on gouty arthritis, respectively. The pharmacokinetic properties and the bioavailability of subcutaneous injection of mPEG-UHC were evaluated in rodents and non-human privates. The elimination half-life of intravenous injection of mPEG-UHC in rats and monkeys were 34.9h and 134.3h. The systemic bioavailability of mPEG-UHC after subcutaneous administration in the above two species is higher than 60%, indicating that subcutaneous injection may be regarded as a candidate administration route. According to 28-day toxicity studies, there were no test article-related effects on clinical observations, hematology and blood biochemistry test. The only treatment-related histopathological changes were the vacuolation of splenic macrophages in one middle-dose (12.5%) and two high-dose (25%) rats, which may be caused by the inducing of anti-PEG IgM antibody and triggering of the uptake of mPEG-UHC by the mononuclear phagocyte system in spleen, but such change did not bring any pathology changes and functional lesions.
This findings not only provide a worthy drug candidate for treating gout, but also represent a valuable resource for understanding the structure and catalytic mechanism of the whole uricase family, the mechanism of accelerated blood clearance triggered by PEGylated proteins and nanoparticles, the elimination mechanism and safety of large PEGylated proteins.
引文
[1]Locatelli F, Rossi F. Incidence and pathogenesis of tumor lysis syndrome. Contrib Nephrol,2005,147:61-68.
[2]Pittman J R, Bross M H. Diagnosis and management of gout. Am Fam Physician, 1999,59(7):1799-1806,1810.
[3]Smyth C J. Disorders associated with hyperuricemia. Arthritis Rheum,1975, 18(6 Suppl):713-719.
[4]Rieselbach R E, Bentzel C J, Cotlove E, Frei E,3rd, Freireich E J. Uric Acid Excretion and Renal Function in the Acute Hyperuricemia of Leukemia. Pathogenesis and Therapy of Uric Acid Nephropathy. Am J Med,1964,37: 872-883.
[5]Terkeltaub R, Bushinsky D A, Becker M A. Recent developments in our understanding of the renal basis of hyperuricemia and the development of novel antihyperuricemic therapeutics. Arthritis Res Ther,2006,8 Suppl 1:S4.
[6]Fox I H. Metabolic basis for disorders of purine nucleotide degradation. Metabolism,1981,30(6):616-634.
[7]Choi H K, Mount D B, Reginato A M. Pathogenesis of gout. Ann Intern Med,2005, 143(7):499-516.
[8]Johnson R J, Rideout B A. Uric acid and diet--insights into the epidemic of cardiovascular disease. N Engl J Med,2004,350(11):1071-1073.
[9]Annemans L, Spaepen E, Gaskin M, Bonnemaire M, Malier V, Gilbert T, Nuki G. Gout in the UK and Germany:prevalence, comorbidities and management in general practice 2000-2005. Ann Rheum Dis,2008,67(7):960-966.
[10]Miao Z, Li C, Chen Y, Zhao S, Wang Y, Wang Z, Chen X, Xu F, Wang F, Sun R, Hu J, Song W, Yan S, Wang C Y. Dietary and lifestyle changes associated with high prevalence of hyperuricemia and gout in the Shandong coastal cities of Eastern China. J Rheumatol,2008,35(9):1859-1864.
[11]Smalley R V, Guaspari A, Haase-Statz S, Anderson S A, Cederberg D, Hohneker J A. Allopurinol:intravenous use for prevention and treatment of hyperuricemia. J Clin Oncol,2000,18(8):1758-1763.
[12]Krakoff I H, Meyer R L. Prevention of Hyperuricemia in Leukemia and Lymphoma: Use of Alopurinol, a Xanthine Oxidase Inhibitor. JAMA,1965,193:1-6.
[13]Greene M L, Fujimoto W Y, Seegmiller J E. Urinary xanthine stones--a rare complications of allopurinol therapy. N Engl J Med,1969,280(8):426-427.
[14]Wyngaarden J B. Allopurinol and xanthine nephropathy. N Engl J Med,1970, 283(7):371-372.
[15]Wortmann R L. Gout and hyperuricemia. Curr Opin Rheumatol,2002,14(3): 281-286.
[16]Yennie R H. Recognition and management of gout and hyperuricemia. JAAPA, 2003,16(3):21-24,27-28,31.
[17]Christen P, Peacock W C, Christen A E, Wacker W E. Urate oxidase in primate phylogenesis. Eur J Biochem,1970,12(1):3-5.
[18]Shnitka T K. Comparative ultrastructure of hepatic microbodies in some mammals and birds in relation to species differences in uricase activity. J Ultrastruct Res,1966,16(5):598-625.
[19]Patte C, Sakiroglu C, Ansoborlo S, Baruchel A, Plouvier E, Pacquement H, Babin-Boilletot A. Urate-oxidase in the prevention and treatment of metabolic complications in patients with B-cell lymphoma and leukemia, treated in the Societe Francaise d'Oncologie Pediatrique LMB89 protocol. Ann Oncol,2002,13(5):789-795.
[20]Cammalleri L, Malaguarnera M. Rasburicase represents a new tool for hyperuricemia in tumor lysis syndrome and in gout. Int J Med Sci,2007,4(2): 83-93.
[21]Schlesinger N, Yasothan U, Kirkpatrick P. Pegloticase. Nat Rev Drug Discov, 2011,10(1):17-18.
[22]Goldman S C, Holcenberg J S, Finklestein J Z, Hutchinson R, Kreissman S, Johnson F L, Tou C, Harvey E, Morris E, Cairo M S. A randomized comparison between rasburicase and allopurinol in children with lymphoma or leukemia at high risk for tumor lysis. Blood,2001,97(10):2998-3003.
[23]Pui C H, Mahmoud H H, Wiley J M, Woods G M, Leverger G, Camitta B, Hastings C, Blaney S M, Relling M V, Reaman G H. Recombinant urate oxidase for the prophylaxis or treatment of hyperuricemia in patients With leukemia or lymphoma. J Cl in Oncol,2001,19(3):697-704.
[24]Pui C H, Relling M V, Lascombes F, Harrison P L, Struxiano A, Mondesir J M, Ribeiro R C, Sandlund J T, Rivera G K, Evans W E, Mahmoud H H. Urate oxidase in prevention and treatment of hyperuricemia associated with lymphoid malignancies. Leukemia,1997,11(11):1813-1816.
[25]Biggers K, Scheinfeld N. Pegloticase, a polyethylene glycol conjugate of uricase for the potential intravenous treatment of gout. Curr Opin Investig Drugs,2008,9(4):422-429.
[26]Retailleau P, Colloc'h N, Vivares D, Bonnete F, Castro B, El-Hajji M, Mornon J P, Monard G, Prange T. Complexed and ligand-free high-resolution structures of urate oxidase (Uox) from Aspergillus flavus:a reassignment of the active-site binding mode. Acta Crystallogr D Biol Crystallogr,2004,60(Pt 3):453-462.
[27]Larsen K. Purification of nodule-specific uricase from soybean by arginine-sepharose affinity chromatography. Prep Biochem,1990,20(1):1-9.
[28]Suzuki H, Verma D P. Soybean Nodule-Specific Uricase (Nodulin-35) Is Expressed and Assembled into a Functional Tetrameric Holoenzyme in Escherichia coli. Plant Physiol,1991,95(2):384-389.
[29]Motojima K, Goto S. Cloning of rabbit uricase cDNA reveals a conserved carboxy-terminal tripeptide in three species. Biochim Biophys Acta,1989, 1008(1):116-118.
[30]Wu X W, Lee C C, Muzny D M, Caskey C T. Urate oxidase:primary structure and evolutionary implications. Proc Natl Acad Sci U S A,1989,86(23): 9412-9416.
[31]Ito M, Suzuki M, Takagi Y. Nucleotide sequence of cDNA and predicted amino acid sequence of rat liver uricase. Eur J Biochem,1988,173(2):459-463.
[32]Suzuki K, Sakasegawa S, Misaki H, Sugiyama M. Molecular cloning and expression of uricase gene from Arthrobacter globiformis in Escherichia coli and characterization of the gene product. J Biosci Bioeng,2004,98(3): 153-158.
[33]Yamamoto K, Kojima Y, Kikuchi T, Shigyo T, Sugihara K, Takashio M, Emi S. Nucleotide sequence of the uricase gene from Bacillus sp. TB-90. J Biochem, 1996,119(1):80-84.
[34]Nishimura H, Yoshida K, Yokota Y, Matsushima A, Inada Y. Physicochemical properties and states of sulfhydryl groups of uricase from Candida utilis. J Biochem,1982,91(1):41-48.
[35]Nguyen T, Zelechowska M, Foster V, Bergmann H, Verma D P. Primary structure of the soybean nodulin-35 gene encoding uricase II localized in the peroxisomes of uninfected cells of nodules. Proc Natl Acad Sci U S A,1985, 82(15):5040-5044.
[36]Goldman B M, Blobel G. Biogenesis of peroxisomes:intracellular site of synthesis of catalase and uricase. Proc Natl Acad Sci U S A,1978,75(10): 5066-5070.
[37]Angermuller S, Fahimi H D. Ultrastructural cytochemical localization of uricase in peroxisomes of rat liver. J Histochem Cytochem,1986,34(2): 159-165.
[38]Antonenkov V D, Grunau S, Ohlmeier S, Hiltunen J K. Peroxisomes are oxidative organelles. Antioxid Redox Signal,2010,13(4):525-537.
[39]Yeldandi A V, Yeldandi V, Kumar S, Murthy C V, Wang X D, Alvares K, Rao M S, Reddy J K. Molecular evolution of the urate oxidase-encoding gene in hominoid primates:nonsense mutations. Gene,1991,109(2):281-284.
[40]Wu X W, Muzny D M, Lee C C, Caskey C T. Two independent mutational events in the loss of urate oxidase during hominoid evolution. J Mol Evol,1992, 34(1):78-84.
[41]Ames B N, Cathcart R, Schwiers E, Hochstein P. Uric acid provides an antioxidant defense in humans against oxidant-and radical-caused aging and cancer:a hypothesis. Proc Natl Acad Sci U S A,1981,78(11):6858-6862.
[42]Cutler R G. Urate and ascorbate:their possible roles as antioxidants in determining longevity of mammalian species. Arch Gerontol Geriatr,1984, 3(4):321-348.
[43]Hooper D C, Scott G S, Zborek A, Mikheeva T, Kean R B, Koprowski H, Spitsin S V. Uric acid, a peroxynitrite scavenger, inhibits CNS inflammation, blood-CNS barrier permeability changes, and tissue damage in a mouse model of multiple sclerosis. FASEB J,2000,14(5):691-698.
[44]Mazzali M, Hughes J, Kim Y G, Jefferson J A, Kang D H, Gordon K L, Lan H Y, Kivlighn S, Johnson R J. Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension,2001,38(5): 1101-1106.
[45]Legoux R, Delpech B, Dumont X, Guillemot J C, Ramond P, Shire D, Caput D, Ferrara P, Loison G. Cloning and expression in Escherichia coli of the gene encoding Aspergillus flavus urate oxidase. J Biol Chem,1992,267(12): 8565-8570.
[46]Chu R, Lin Y, Usuda N, Rao M S, Reddy J K, Yeldandi A V. Mutational analysis of the putative copper-binding site of rat urate oxidase. Ann N Y Acad Sci, 1996,804:781-786.
[47]Miura S, Oda T, Funai T, Ito M, Okada Y, Ichiyama A. Urate oxidase is imported into peroxisomes recognizing the C-terminal SKL motif of proteins. Eur J Biochem,1994,223(1):141-146.
[48]Colloc'h N, el Hajji M, Bachet B, L'Hermite G, Schiltz M, Prange T, Castro B, Mornon J P. Crystal structure of the protein drug urate oxidase-inhibitor complex at 2.05 A resolution. Nat Struct Biol,1997,4(11):947-952.
[49]Burgisser D M, Thony B, Redweik U, Hess D, Heizmann C W, Huber R, Nar H. 6-Pyruvoyl tetrahydropterin synthase, an enzyme with a novel type of active site involving both zinc binding and an intersubunit catalytic triad motif; site-directed mutagenesis of the proposed active center, characterization of the metal binding site and modelling of substrate binding. J Mol Biol, 1995,253(2):358-369.
[50]Ploom T, Haussmann C, Hof P, Steinbacher S, Bacher A, Richardson J, Huber R. Crystal structure of 7,8-dihydroneopterin triphosphate epimerase. Structure,1999,7(5):509-516.
[51]Nar H, Huber R, Auerbach G, Fischer M, Hosl C, Ritz H, Bracher A, Meining W, Eberhardt S, Bacher A. Active site topology and reaction mechanism of GTP cyclohydrolase I. Proc Natl Acad Sci U S A,1995,92(26):12120-12125.
[52]Colloc'h N, Mornon J P, Camadro J M. Towards a new T-fold protein?:the coproporphyrinogen III oxidase sequence matches many structural features from urate oxidase. FEBS Lett,2002,526(1-3):5-10.
[53]Colloc'h N, Poupon A, Mornon J P. Sequence and structural features of the T-fold, an original tunnelling building unit. Proteins,2000,39(2): 142-154.
[54]Juan E C, Hoque M M, Shimizu S, Hossain M T, Yamamoto T, Imamura S, Suzuki K, Tsunoda M, Amano H, Sekiguchi T, Takenaka A. Structures of Arthrobacter globiformis urate oxidase-ligand complexes. Acta Crystallogr D Biol Crystallogr,2008, D64(Pt 8):815-822.
[55]Lucas K, Boland M J, Schubert K R. Uricase from soybean root nodules: purification, properties, and comparison with the enzyme from cowpea. Arch Biochem Biophys,1983,226(1):190-197.
[56]Szasz T, Watts S W. Uric acid does not affect the acetylcholine-induced relaxation of aorta from normotensive and deoxycorticosterone acetate-salt hypertensive rats. J Pharmacol Exp Ther,2010,333(3):758-763.
[57]Bayol A, Capdevielle J, Malazzi P, Buzy A, Claude Bonnet M, Colloc'h N, Mornon J P, Loyaux D, Ferrara P. Modification of a reactive cysteine explains differences between rasburicase and Uricozyme, a natural Aspergillus flavus uricase. Biotechnol Appl Biochem,2002,36(Pt 1):21-31.
[58]Hershfield M S, Kelly S J. Urate oxidase.2006.
[59]Varela-Echavarria A, Montes de Oca-Luna R, Barrera-Saldana H A. Uricase protein sequences:conserved during vertebrate evolution but absent in humans. FASEB J,1988,2(15):3092-3096.
[60]Gabison L, Prange T, Colloc'h N, El Hajji M, Castro B, Chiadmi M. Structural analysis of urate oxidase in complex with its natural substrate inhibited by cyanide:mechanistic implications. BMC Struct Biol,2008,8:32.
[61]Colloc'h N, Gabison L, Monard G, Altarsha M, Chiadmi M, Marassio G, Sopkova-de Oliveira Santos J, El Hajji M, Castro B, Abraini J H, Prange T. Oxygen pressurized X-ray crystallography:probing the dioxygen binding site in cofactorless urate oxidase and implications for its catalytic mechanism. Biophys J,2008,95(5):2415-2422.
[62]Duff A P, Trambaiolo D M, Cohen A E, Ellis P J, Juda G A, Shepard E M, Langley D B, Dooley D M, Freeman H C, Guss J M. Using xenon as a probe for dioxygen-binding sites in copper amine oxidases. J Mol Biol,2004,344(3): 599-607.
[63]Tilton R F, Jr., Kuntz I D, Jr., Petsko G A. Cavities in proteins:structure of a metmyoglobin-xenon complex solved to 1.9 A. Biochemistry,1984,23(13): 2849-2857.
[64]Wade R C, Winn P J, Schlichting I, Sudarko. A survey of active site access channels in cytochromes P450. J Inorg Biochem,2004,98(7):1175-1182.
[65]Hiromoto T, Fujiwara S, Hosokawa K, Yamaguchi H. Crystal structure of 3-hydroxybenzoate hydroxylase from Comamonas testosteroni has a large tunnel for substrate and oxygen access to the active site. J Mol Biol,2006,364(5): 878-896.
[66]Bentley R, Neuberger A. The mechanism of the action of uricase. Biochem J, 1952,52(4):694-699.
[67]Sokolic L, Modric N, Poje M. Regiochemical course of chemical and enzymic uricolysis to allantoin. A non-degradative 13C-NMR evidence. Tetrahedron Lett,1991,32:7477-7480.
[68]Kahn K, Tipton P A. Spectroscopic characterization of intermediates in the urate oxidase reaction. Biochemistry,1998,37(33):11651-11659.
[69]Frerichs-Deeken U, Ranguelova K, Kappl R, Huttermann J, Fetzner S. Dioxygenases without requirement for cofactors and their chemical model reaction:compulsory order ternary complex mechanism of 1H-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase involving general base catalysis by histidine 251 and single-electron oxidation of the substrate dianion. Biochemistry,2004,43(45):14485-14499.
[70]Sciara G, Kendrew S G, Miele A E, Marsh N G, Federici L, Malatesta F, Schimperna G, Savino C, Vallone B. The structure of ActVA-0rf6, a novel type of monooxygenase involved in actinorhodin biosynthesis. EMBO J,2003,22(2): 205-215.
[71]Fetzner S. Oxygenases without requirement for cofactors or metal ions. Appl Microbiol Biotechnol,2002,60(3):243-257.
[72]Roda A, Parisi D, Guardigli M, Zattoni A, Reschiglian P. Combined approach to the analysis of recombinant protein drugs using hollow-fiber flow field-flow fractionation, mass spectrometry, and chemiluminescence detection. Anal Chem,2006,78(4):1085-1092.
[73]Marli L M, Ubirajara P, Rodrigues F, Osvaldo N, Oliveira J, Marystela F. Immobilization of uricase in layer-by-layer films used in amperometric biosensors for uric acid J Solid State Electrochem,2007,11(1):1489-1495.
[74]Montalbini P, Aguilar M, Pineda M. Isolation and characterization of uricase from bean leaves and its comparison with uredospore enzymes. Plant Sci,1999, 147(2):139-147.
[75]Kelly S J, Delnomdedieu M, Oliverio M I, Williams L D, Saifer M G, Sherman M R, Coffman T M, Johnson G A, Hershfield M S. Diabetes insipidus in uricase-deficient mice:a model for evaluating therapy with poly(ethylene glycol)-modified uricase. J Am Soc Nephrol,2001,12(5):1001-1009.
[76]Kahn K, Tipton P A. Kinetic mechanism and cofactor content of soybean root nodule urate oxidase. Biochemistry,1997,36(16):4731-4738.
[77]Shekarriz B, Stoller M L. Uric acid nephrolithiasis:current concepts and controversies. J Urol,2002,168(4 Pt 1):1307-1314.
[78]Tokimitsu Y, Ise N, Tanaka D, Kunugi S. Uricase Model Reactions of Polylysine-Cu(Ⅱ) Complexes. Bull Chem Soc Jpn,1995,68:3277-3282.
[79]Hinberg I, O'Driscoll K F. Preparation and kinetic properties of gel entrapped urate oxidase. Biotechnol Bioeng,1975,17(10):1435-1441.
[80]Liu J, Li G, Liu H, Zhou X. Purification and properties of uricase from Candida sp. and its application in uric acid analysis in serum. Appl Biochem Biotechnol,1994,47(1):57-63.
[81]Ohe T, Watanabe Y. Purification and properties of urate oxidase from Streptomyces cyanogenus. J Biochem,1981,89(6):1769-1776.
[82]Itaya K, Yamamoto T, Fukumoto J. Studies on yeast uricase. Part I. Purification and some enzymatic properties of yeast uricase. Agric Biol Chem, 1967,31:1256-1264.
[83]Adamek V, Kralova B, Suchova M, Valentova 0, Demnerova K. Purification of microbial uricase. J Chromatogr,1989,497:268-275.
[84]Bongaerts G P, Uitzetter J, Brouns R, Vogels G D. Uricase of Bacillus fastidiosus. Properties and regulation of synthesis. Biochim Biophys Acta, 1978,527(2):348-358.
[85]Bentley K W, Truscoe R. Effect of treatment with dithiothreitol on the extraction, activity and purification of ox-kidney urate oxidase. Enzymologia,1969,37:131-152.
[86]Conley T G, Priest D G. Purification of uricase from mammalian tissue. Prep Biochem,1979,9(2):197-203.
[87]London M, Hudson P B. Uricolytic activity of purified uricase in two human beings. Science,1957,125(3254):937-938.
[88]Machida Y, Nakanishi T. Purification and properties of uricae from Enterobacter cloacae. Agric Biol Chem,1980,44:2811-2815.
[89]Nishiya Y, Hibi T, Oda J. A purification method of the diagnostic enzyme Bacillus uricase using magnetic beads and non-specific protease. Protein Expr Purif,2002,25(3):426-429.
[90]Greenberg M L, Hershfield M S. A radiochemical-high-performance liquid chromatographic assay for urate oxidase in human plasma. Anal Biochem,1989, 176(2):290-293.
[91]Haeckel R. The use of aldehyde dehydrogenase to determine H202-producing reactions. I. The determination of the uric acid concentration. J Clin Chem Clin Biochem,1976,14(3):101-107.
[92]Kageyama N. A direct colorimetric determination of uric acid in serum and urine with uricase-catalase system. Clin Chim Acta,1971,31(2):421-426.
[93]Fossati P, Prencipe L, Berti G. Use of 3,5-dichloro-2-hydroxybenzenesulfonic acid/4-aminophenazone chromogenic system in direct enzymic assay of uric acid in serum and urine. Clin Chem, 1980,26(2):227-231.
[94]Hasebe Y, Nawa K, Ujita S, Uchiyama S. Highly sensitive flow detection of uric acid based on an intermediate regeneration of uricase. Analyst,1998, 123(8):1775-1780.
[95]Tao H, Wang X, Hu Y, Ma Y, Lu Y, Hu Z. Construction of uric acid biosensor based on biomimetic titanate nanotubes. J Nanosci Nanotechnol,2010,10(2): 860-864.
[96]Roberts M J, Bentley M D, Harris J M. Chemistry for peptide and protein PEGylation. Adv Drug Deliv Rev,2002,54(4):459-476.
[97]Veronese F M, Mero A, Pasut G. Protein PEGylation, basic science and biological applications. Veronese F M. PEGylated Protein Durgs:Basic Science and Clinical Application. [C].2009.11-31.
[98]Veronese F M. Peptide and protein PEGylation:a review of problems and solutions. Biomaterials,2001,22(5):405-417.
[99]Harris J M, Chess R B. Effect of pegylation on pharmaceuticals. Nat Rev Drug Discov,2003,2(3):214-221.
[100]Zalipsky S. Chemistry of polyethylene glycol conjugates with biologically active molecules. Adv Drug Deliv Rev,1995,16:157-182.
[101]Ensor C M, Clark M A, Holtsbege F W. PEG-modified Uricase.2003.
[102]Kang J S, Deluca P P, Lee K C. Emerging PEGylated drugs. Expert Opin Emerg Drugs,2009,14(2):363-380.
[103]Kartre K. The conjugation of proteins with poly(ethylene glyclo) and other polymers. Adv Drug Deliv Rev,1993,10:91-114.
[104]Brenner B M, Hostetter T H, Humes H D. Glomerular permselectivity:barrier function based on discrimination of molecular size and charge. Am J Physiol, 1978,234(6):F455-460.
[105]Takakura Y, Fujita T, Hashida M, Sezaki H. Disposition characteristics of macromolecules in tumor-bearing mice. Pharm Res,1990,7(4):339-346.
[106]Venkatachalam M A, Rennke H G. The structural and molecular basis of glomerular filtration. Circ Res,1978,43(3):337-347.
[107]Sherman M R, Williams L D, Saifer M C P, French J A, Kwak L W, Oppenheim J J. Conjugation of high, molecular weight poly(ethylene glycol) to cytokines:granulocytemacrophage colony stimulating factors as model substrates. Harris J M, and Zalipsky S. Poly (Ethylene Glycol):Chemistry and Biological Application[C]. Washington, DC:ACS,1997.155.
[108]Molineux G. The design and development of pegfilgrastim (PEG-rmetHuG-CSF, Neulasta). Curr Pharm Des,2004,10(11):1235-1244.
[109]Veronese F M, Monfardini C, Caliceti P, Schiavon 0, Scrawen M D, Beer D. Improvement of pharmacokinetic, immunological and stability properties of asparginase by conjugation of linear and branched monomethoxy poly (ethylene glycol). J Control Release,1996,40(3):199-209.
[110]Caliceti P, Schiavon 0, Veronese F M. Immunological properties of uricase conjugated to neutral soluble polymers. Bioconjug Chem,2001,12(4): 515-522.
[111]Kompella U B, Lee V H L. Pharmacokinetics of peptide and protein drugs. Lee V H L. Peptide and Protein Drug Delivery[C].New York:Marcel Dekker, 1991.391.
[112]Conover C D, Gilbert C W, Shum K L, Shorr R G. The impact of polyethylene glycol conjugation on bovine hemoglobin's circulatory half-life and renal effects in a rabbit top-loaded transfusion model. Artif Organs,1997,21: 907-915.
[113]Caliceti P, Schiavon 0, Veronese F M. Biopharmaceutical properties of uricase conjugated to neutral and amphiphilic polymers. Bioconjug Chem, 1999,10(4):638-646.
[114]Williams D L F, CA), Hershfield, Michael S. (Durham, NC), Kelly, Susan J. (Chapel Hill, NC), Saifer, Mark G. P. (San Carlos, CA), Sherman, Merry R. (San Carlos, CA). PEG-urate oxidase conjugates and use thereof.2003, 6576235.
[115]Nishimura H, Ashihara Y, Matsushima A, Inada Y. Modification of yeast uricase with polyethylene glycol:disappearance of binding ability towards anti-uricase serum. Enzyme,1979,24(4):261-264.
[116]Nishimura H, Matsushima A, Inada Y. Improved modification of yeast uricase with polyethylene glycol, accompanied with nonimmunoreactivity towards anti-uricase serum and high enzymic activity. Enzyme,1981,26(1):49-53.
[117]Abuchowski A, Karp D, Davis F F. Reduction of plasma urate levels in the cockerel with polyethylene glycol-uricase. J Pharmacol Exp Ther,1981, 219(2):352-354.
[118]Chen R H, Abuchowski A, Van Es T, Palczuk N C, Davis F F. Properties of two urate oxidases modified by the covalent attachment of poly(ethylene glycol). Biochim Biophys Acta,1981,660(2):293-298.
[119]Tsuji J, Hirose K, Kasahara E, Naitoh M, Yamamoto I. Studies on antigenicity of the polyethylene glycol (PEG)-modified uricase. Int J Immunopharmacol, 1985,7(5):725-730.
[120]Chua C C, Greenberg M L, Viau A T, Nucci M, Brenckman W D, Jr., Hershfield M S. Use of polyethylene glycol-modified uricase (PEG-uricase) to treat hyperuricemia in a patient with non-Hodgkin lymphoma. Ann Intern Med,1988, 109(2):114-117.
[121]Yasuda Y, Fujita T, Takakura Y, Hashida M, Sezaki H. Biochemical and biopharmaceutical properties of macromolecular conjugates of uricase with dextran and polyethylene glycol. Chem Pharm Bull (Tokyo),1990,38(7): 2053-2056.
[122]Fujita T, Yasuda Y, Takakura Y, Hashida M, Sezaki H. Tissue distribution of 111In-labeled uricase conjugated with charged dextrans and polyethylene glycol. J Pharmacobiodyn,1991,14(11):623-629.
[123]Ganson N J, Kelly S J, Scarlett E, Sundy J S, Hershfield M S. Control of hyperuricemia in subjects with refractory gout, and induction of antibody against poly(ethylene glycol) (PEG), in a phase I trial of subcutaneous PEGylated urate oxidase. Arthritis Res Ther,2006,8(1):R12.
[124]Baraf H S, Matsumoto A K, Maroli A N, Waltrip R W,2nd. Resolution of gouty tophi after twelve weeks of pegloticase treatment. Arthritis Rheum,2008, 58(11):3632-3634.
[125]Young M A, Malavalli A, Winslow N, Vandegriff K D, Winslow R M. Toxicity and hemodynamic effects after single dose administration of MalPEG-hemoglobin (MP4) in rhesus monkeys. Transl Res,2007,149(6): 333-342.
[126]Savient Pharmaceuticals I. KrystexxaTM(petloticase) Injection, for intravenous infusion. http://wwwkrystexxacom/pdfs/KRYSTEXXA Prescribing_Informationpdf,2010.
[127]Bomalaski J S, Goddard D H, Grezlak D. Phase I study of uricase formulated with polyethylene glycol (Uricase-PEG 20). Arthritis Rheum,2002,46(suppl): S141.
[128]Bomalaski J S, Clark M A. Serum uric acid-lowering therapies:where are we heading in management of hyperuricemia and the potential role of uricase. Curr Rheumatol Rep,2004,6 (3):240-247.
[129]Bomalaski J S, Holtsberg F W, Ensor C M, Clark M A. Uricase formulated with polyethylene glycol (uricase-PEG 20):biochemical rationale and preclinical studies. J Rheumatol,2002,29(9):1942-1949.
[130]Ensor C M L, KY, US), Clark, Mike A. (Lexington, KY, US), Holtsberg, Frederick Wayne (Nicholasville, KY, US). PEG-modified uricase.2005, 6913915.
[131]Pui C H. Urate oxidase in the prophylaxis or treatment of hyperuricemia: the United States experience. Semin Hematol,2001,38(4 Suppl 10):13-21.
[132]Sherman M R, Saifer M G, Perez-Ruiz F. PEG-uricase in the management of treatment-resistant gout and hyperuricemia. Adv Drug Deliv Rev,2008,60(1): 59-68.
[133]Lu G, Moriyama E N. Vector NTI, a balanced all-in-one sequence analysis suite. Brief Bioinform,2004,5(4):378-388.
[134]Truszkowski R, Goldmanowna C. Uricase and its action:Distribution in various animals. Biochem J,1933,27(3):612-614.
[135]Safra N, Ling G V, Schaible R H, Bannasch D L. Exclusion of urate oxidase as a candidate gene for hyperuricosuria in the Dalmatian dog using an interbreed backcross. J Hered,2005,96(7):750-754.
[136]0da M, Satta Y, Takenaka 0, Takahata N. Loss of urate oxidase activity in hominoids and its evolutionary implications. Mol Biol Evol,2002,19(5): 640-653.
[137]Lee C C, Wu X W, Gibbs R A, Cook R G, Muzny D M, Caskey C T. Generation of cDNA probes directed by amino acid sequence:cloning of urate oxidase. Science,1988,239(4845):1288-1291.
[138]Karplus K. SAM-T08, HMM-based protein structure prediction. Nucleic Acids Res,2009,37(Web Server issue):W492-497.
[139]Lee H J, Wilson I B. Enzymic parameters:measurement of V and Km. Biochim Biophys Acta,1971,242(3):519-522.
[140]Gabison L, Chiadmi M, El Hajji M, Castro B, Colloc'h N, Prange T. Near-atomic resolution structures of urate oxidase complexed with its substrate and analogues:the protonation state of the ligand. Acta Crystallogr D Biol Crystallogr,2010,66(Pt 6):714-724.
[141]Guex N, Peitsch M C. SWISS-MODEL and the Swiss-PdbViewer:an environment for comparative protein modeling. Electrophoresis,1997,18(15): 2714-2723.
[142]Retailleau P, Colloc'h N, Vivares D, Bonnete F, Castro B, ElHajji M, Prange T. Urate oxidase from Aspergillus flavus:new crystal-packing contacts in relation to the content of the active site. Acta Crystallogr D Biol Crystallogr,2005,61 (Pt 3):218-229.
[143]Wu Y, Cao Z, Yi H, Jiang D, Mao X, Liu H, Li W. Simulation of the interaction between ScyTx and small conductance calcium-activated potassium channel by docking and MM-PBSA. Biophys J,2004,87(1):105-112.
[144]Jin L, Wu Y. Molecular mechanism of the sea anemone toxin ShK recognizing the Kvl.3 channel explored by docking and molecular dynamic simulations. J Chem Inf Model,2007,47(5):1967-1972.
[145]Allinger N L. Conformational analysis.130. MM2. A hydrocarbon force field utilizing V1 and V2 torsional terms. J Am Chem Soc,1977,99(25):8127-8134.
[146]Friesner R A, Banks J L, Murphy R B, Halgren T A, Klicic J J, Mainz D T, Repasky M P, Knoll E H, Shelley M, Perry J K, Shaw D E, Francis P, Shenkin P S. Glide:a new approach for rapid, accurate docking and scoring.1. Method and assessment of docking accuracy. J Med Chem,2004,47(7):1739-1749.
[147]Halgren T A, Murphy R B, Friesner R A, Beard H S, Frye L L, Pollard W T, Banks J L. Glide:a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. J Med Chem,2004,47(7): 1750-1759.
[148]Tsui V, Case D A. Theory and applications of the generalized Born solvation model in macromolecular simulations. Biopolymers,2000,56(4):275-291.
[149]Wang J, Cieplak P, Kollman P. How well does a restrained electrostatic potential (RESP) model perform in calculating conformational energies of organic and biological molecules? J Comput Chem,2000,21:1049-1074.
[150]Laskowski R A, MacArthur M W, Moss D S, Thornton J M. PROCHECK:a program to check the stereochemical quality of protein structures.. J App Crystallogr,1993,26:283-291.
[151]Guex N, Peitsch M C, Schwede T. Automated comparative protein structure modeling with SWISS-MODEL and Swiss-PdbViewer:a historical perspective. Electrophoresis,2009,30 Suppl 1:S162-173.
[152]Pahwa S, Kaur S, Jain R, Roy N. Structure based design of novel inhibitors for histidinol dehydrogenase from Geotrichum candidum. Bioorg Med Chem Lett, 2010,20(13):3972-3976.
[153]Ellman G L. Tissue sulfhydryl groups. Arch Biochem Biophys,1959,82(1): 70-77.
[154]Saitou N, Nei M. The neighbor-joining method:a new method for reconstructing phylogenetic trees. Mol Biol Evol,1987,4(4):406-425.
[155]Studier F W. Use of bacteriophage T7 lysozyme to improve an inducible T7 expression system. J Mol Biol,1991,219(1):37-44.
[156]Wedemeyer W J, Welker E, Narayan M, Scheraga H A. Disulfide bonds and protein folding. Biochemistry,2000,39(15):4207-4216.
[157]Imhoff R D, Power N P, Borrok M J, Tipton P A. General base catalysis in the urate oxidase reaction:evidence for a novel Thr-Lys catalytic diad. Biochemistry,2003,42(14):4094-4100.
[158]Lunelli M, Di Paolo M L, Biadene M, Calderone V, Battistutta R, Scarpa M, Rigo A, Zanotti G. Crystal structure of amine oxidase from bovine serum. J Mol Biol,2005,346(4):991-1004.
[159]Colloc'h N, Girard E, Dhaussy A C, Kahn R, Ascone I, Mezouar M, Fourme R. High pressure macromolecular crystallography:the 140-MPa crystal structure at 2.3 A resolution of urate oxidase, a 135-kDa tetrameric assembly. Biochim Biophys Acta,2006,1764(3):391-397.
[160]Poupon A, Mornon J P. Populations of hydrophobic amino acids within protein globular domains:identification of conserved "topohydrophobic" positions. Proteins,1998,33(3):329-342.
[161]Riddles P W, Blakeley R L, Zerner B. Ellman's reagent: 5,5'-dithiobis (2-nitrobenzoic acid)--a reexamination. Anal Biochem,1979, 94(1):75-81.
[162]Schrader M, Fahimi H D. The peroxisome:still a mysterious organelle. Histochem Cell Biol,2008,129(4):421-440.
[163]Rosenberg A S. Effects of protein aggregates:an immunologic perspective. AAPS J,2006,8(3):E501-507.
[164]Caliceti P, Veronese F M. Pharmacokinetic and biodistribution properties of poly (ethylene glycol)-protein conjugates. Adv Drug Deliv Rev,2003, 55(10):1261-1277.
[165]Hershfield M S. Adenosine deaminase deficiency:clinical expression, molecular basis, and therapy. Semin Hematol,1998,35(4):291-298.
[166]Pasut G, Sergi M, Veronese F M. Anti-cancer PEG-enzymes:30 years old, but still a current approach. Adv Drug Deliv Rev,2008,60(1):69-78.
[167]Parkinson C, Scarlett J A, Trainer P J. Pegvisomant in the treatment of acromegaly. Adv Drug Deliv Rev,2003,55(10):1303-1314.
[168]Freitas Dda S, Spencer P J, Vassao R C, Abrahao-Neto J. Biochemical and biopharmaceutical properties of PEGylated uricase. Int J Pharm,2010, 387(1-2):215-222.
[169]Fee C J, Van Alstine J M. Prediction of the viscosity radius and the size exclusion chromatography behavior of PEGylated proteins. Bioconjug Chem, 2004,15(6):1304-1313.
[170]Habeeb A F. Determination of free amino groups in proteins by trinitrobenzenesulfonic acid. Anal Biochem,1966,14(3):328-336.
[171]Li J, Kao W J. Synthesis of polyethylene glycol (PEG) derivatives and PEGylated-peptide biopolymer conjugates. Biomacromolecules,2003,4(4): 1055-1067.
[172]Greenfield N J. Using circular dichroism spectra to estimate protein secondary structure. Nat Protoc,2006,1 (6):2876-2890.
[173]Sundy J S, Ganson N J, Kelly S J, Scarlett E L, Rehrig C D, Huang W, Hershfield M S. Pharmacokinetics and pharmacodynamics of intravenous PEGylated recombinant mammalian urate oxidase in patients with refractory gout. Arthritis Rheum,2007,56(3):1021-1028.
[174]Rajender Reddy K, Modi M W, Pedder S. Use of peginterferon alfa-2a (40 KD) (Pegasys) for the treatment of hepatitis C. Adv Drug Deliv Rev,2002,54(4): 571-586.
[175]Bruno R, Sacchi P, Ciappina V, Zochetti C, Patruno S, Maiocchi L, Filice G. Viral dynamics and pharmacokinetics of peginterferon alpha-2a and peginterferon alpha-2b in naive patients with chronic hepatitis c:a randomized, controlled study. Antivir Ther,2004,9(4):491-497.
[176]Schiavon 0, Caliceti P, Ferruti P, Veronese F M. Therapeutic proteins:a comparison of chemical and biological properties of uricase conjugated to linear or branched poly (ethylene glycol) and poly(N-acryloylmorpholine). Farmaco,2000,55 (4):264-269.
[177]Harris M J, Kozlowski A. Poly(ethylene glycol) and related polymers monosubstituted with propionic or butanoic acids and functional derivatives thereof for biotechnical applications.1997,5672662.
[178]Wu M, Dellacherie E, Durand A, Marie E. Poly(n-butyl cyanoacrylate) nanoparticles via miniemulsion polymerization.2. PEG-based surfactants. Colloids Surf B Biointerfaces,2009,69(1):147-151.
[179]Horisberger M, Rosset J. Colloidal gold, a useful marker for transmission and scanning electron microscopy. J Histochem Cytochem,1977,25(4): 295-305.
[180]Hoiseth G, Bernard J P, Karinen R, Johnsen L, Helander A, Christophersen A S, Morland J. A pharmacokinetic study of ethyl glucuronide in blood and urine:applications to forensic toxicology. Forensic Sci Int,2007, 172(2-3):119-124.
[181]Kozlowski A, Charles S A, Harris J M. Development of PEGylated interferons for the treatment of chronic hepatitis C. BioDrugs,2001,15(7):419-429.
[182]Cheng T L, Wu P Y, Wu M F, Chern J W, Roffler S R. Accelerated clearance of polyethylene glycol-modified proteins by anti-polyethylene glycol IgM. Bioconjug Chem,1999,10(3):520-528.
[183]Ishida T, Masuda K, Ichikawa T, Ichihara M, Irimura K, Kiwada H. Accelerated clearance of a second injection of PEGylated liposomes in mice. Int J Pharm, 2003,255(1-2):167-174.
[184]Ishida T, Maeda R, Ichihara M, Irimura K, Kiwada H. Accelerated clearance of PEGylated liposomes in rats after repeated injections. J Control Release, 2003,88(1):35-42.
[185]Ishida T, Ichihara M, Wang X, Yamamoto K, Kimura J, Majima E, Kiwada H. Injection of PEGylated liposomes in rats elicits PEG-specific IgM, which is responsible for rapid elimination of a second dose of PEGylated liposomes. J Control Release,2006,112(1):15-25.
[186]Wang X, Ishida T, Kiwada H. Anti-PEG IgM elicited by injection of liposomes is involved in the enhanced blood clearance of a subsequent dose of PEGylated liposomes. J Control Release,2007,119(2):236-244.
[187]Koide H, Asai T, Hatanaka K, Akai S, Ishii T, Kenjo E, Ishida T, Kiwada H, Tsukada H, Oku N. T cell-independent B cell response is responsible for ABC phenomenon induced by repeated injection of PEGylated liposomes. Int J Pharm,2010,392(1-2):218-223.
[188]Ishihara T, Takeda M, Sakamoto H, Kimoto A, Kobayashi C, Takasaki N, Yuki K, Tanaka K, Takenaga M, Igarashi R, Maeda T, Yamakawa N, Okamoto Y, Otsuka M, Ishida T, Kiwada H, Mizushima Y, Mizushima T. Accelerated blood clearance phenomenon upon repeated injection of PEG-modified PLA-nanoparticles. Pharm Res,2009,26(10):2270-2279.
[189]Ishida T, Wang X, Shimizu T, Nawata K, Kiwada H. PEGylated liposomes elicit an anti-PEG IgM response in a T cell-independent manner. J Control Release, 2007,122(3):349-355.
[190]Ishida T, Kashima S, Kiwada H. The contribution of phagocytic activity of liver macrophages to the accelerated blood clearance (ABC) phenomenon of PEGylated liposomes in rats. J Control Release,2008,126(2):162-165.
[191]Ishida T, Harada M, Wang X Y, Ichihara M, Irimura K, Kiwada H. Accelerated blood clearance of PEGylated liposomes following preceding liposome injection:effects of lipid dose and PEG surface-density and chain length of the first-dose liposomes. J Control Release,2005,105(3):305-317.
[192]Ishida T, Kiwada H. Accelerated blood clearance (ABC) phenomenon upon repeated injection of PEGylated liposomes. Int J Pharm,2008,354(1-2): 56-62.
[193]Wang X Y, Ishida T, Ichihara M, Kiwada H. Influence of the physicochemical properties of liposomes on the accelerated blood clearance phenomenon in rats. J Control Release,2005,104(1):91-102.
[194]Efremova N T, Sheth S R, Leckband D E. Protein-induced change in poly(ethylene glycol) brushes:molecular weight and temperature difference. Langmuir,2001,17:7628-7636.
[195]Stavric B, Johnson W J, Grice H C. Uric acid nephropathy:an experimental model. Proc Soc Exp Biol Med,1969,130(2):512-516.
[196]Coderre T J, Wall P D. Ankle joint urate arthritis in rats provides a useful tool for the evaluation of analgesic and anti-arthritic agents. Pharmacol Biochem Behav,1988,29(3):461-466.
[197]Frui jtier-Polloth C. Safety assessment on polyethylene glycols (PEGs) and their derivatives as used in cosmetic products. Toxicology,2005,214(1-2): 1-38.
[198]Webster R, Didier E, Harris P, Siegel N, Stadler J, Tilbury L, Smith D. PEGylated proteins:evaluation of their safety in the absence of definitive metabolism studies. Drug Metab Dispos,2007,35(1):9-16.
[199]Keebaugh A C, Thomas J W. The evolutionary fate of the genes encoding the purine catabolic enzymes in hominoids, birds, and reptiles. Mol Biol Evol, 2010,27(6):1359-1369.
[200]Wu X, Wakamiya M, Vaishnav S, Geske R, Montgomery C, Jr., Jones P, Bradley A, Caskey C T. Hyperuricemia and urate nephropathy in urate oxidase-deficient mice. Proc Natl Acad Sci U S A,1994,91(2):742-746.
[201]Monrad S U, Killen P D, Anderson M R, Bradke A, Kaplan M J. The role of aldosterone blockade in murine lupus nephritis. Arthritis Res Ther,2008, 10(1):R5.
[202]Ekundi-Valentim E, Santos K T, Camargo E A, Denadai-Souza A, Teixeira S A, Zanoni C I, Grant A D, Wallace J, Muscara M N, Costa S K. Differing effects of exogenous and endogenous hydrogen sulphide in carrageenan-induced knee joint synovitis in the rat. Br J Pharmacol,2010,159(7):1463-1474.
[203]Edwards C K,3rd. PEGylated recombinant human soluble tumour necrosis factor receptor type I (r-Hu-sTNF-RI):novel high affinity TNF receptor designed for chronic inflammatory diseases. Ann Rheum Dis,1999,58 Suppl 1:173-81.
[204]Roth A, Mollenhauer J, Wagner A, Fuhrmann R, Straub A, Venbrocks R A, Petrow P, Brauer R, Schubert H, Ozegowski J, Peschel G, Muller P J, Kinne R W. Intra-articular injections of high-molecular-weight hyaluronic acid have biphasic effects on joint inflammation and destruction in rat antigen-induced arthritis. Arthritis Res Ther,2005,7(3):R677-686.
[205]Nolen R S. Revision process begins for AVMA euthanasia guidelines. J Am Vet Med Assoc,2009,235(3):246-247.
[206]Liebman S E, Taylor J G, Bushinsky D A. Uric acid nephrolithiasis. Curr Rheumatol Rep,2007,9(3):251-257.
[207]Schlesinger N. Management of acute and chronic gouty arthritis:present state-of-the-art. Drugs,2004,64(21):2399-2416.
[208]Edwards C K,3rd, Martin S W, Seely J, Kinstler 0, Buckel S, Bendele A M, Ellen Cosenza M, Feige U, Kohno T. Design of PEGylated soluble tumor necrosis factor receptor type I (PEG sTNF-RI) for chronic inflammatory diseases. Adv Drug Deliv Rev,2003,55(10):1315-1336.
[209]Gabay C. Cytokine inhibitors in the treatment of rheumatoid arthritis. Expert Opin Biol Ther,2002,2(2):135-149.
[210]Conover C, Lejeune L, Linberg R, Shum K, Shorr R G. Transitional vacuole formation following a bolus infusion of PEG-hemoglobin in the rat. Artif Cells Blood Substit Immobil Biotechnol,1996,24(6):599-611.
[211]Shum K L, Leon A, Viau A T, Pilon D, Nucci M, Shorr R G. The physiological and histopathological response of dogs to exchange transfusion with polyethylene glycol-modified bovine hemoglobin (PEG-Hb). Artif Cells Blood Substit Immobil Biotechnol,1996,24(6):655-683.
[212]Viau A T, Abuchowski A, Greenspan S, Davis F F. Safety evaluation of free radical scavengers PEG-catalase and PEG-superoxide dismutase. J Free Radic Biol Med,1986,2(4):283-288.
[213]Schaer D J, Schaer C A, Buehler P W, Boykins R A, Schoedon G, Alayash A I, Schaffner A. CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin. Blood,2006, 107(1):373-380.
[2]Pittman J R, Bross M H. Diagnosis and management of gout. Am Fam Physician, 1999,59(7):1799-1806,1810.
[3]Smyth C J. Disorders associated with hyperuricemia. Arthritis Rheum,1975, 18(6 Suppl):713-719.
[4]Rieselbach R E, Bentzel C J, Cotlove E, Frei E,3rd, Freireich E J. Uric Acid Excretion and Renal Function in the Acute Hyperuricemia of Leukemia. Pathogenesis and Therapy of Uric Acid Nephropathy. Am J Med,1964,37: 872-883.
[5]Terkeltaub R, Bushinsky D A, Becker M A. Recent developments in our understanding of the renal basis of hyperuricemia and the development of novel antihyperuricemic therapeutics. Arthritis Res Ther,2006,8 Suppl 1:S4.
[6]Fox I H. Metabolic basis for disorders of purine nucleotide degradation. Metabolism,1981,30(6):616-634.
[7]Choi H K, Mount D B, Reginato A M. Pathogenesis of gout. Ann Intern Med,2005, 143(7):499-516.
[8]Johnson R J, Rideout B A. Uric acid and diet--insights into the epidemic of cardiovascular disease. N Engl J Med,2004,350(11):1071-1073.
[9]Annemans L, Spaepen E, Gaskin M, Bonnemaire M, Malier V, Gilbert T, Nuki G. Gout in the UK and Germany:prevalence, comorbidities and management in general practice 2000-2005. Ann Rheum Dis,2008,67(7):960-966.
[10]Miao Z, Li C, Chen Y, Zhao S, Wang Y, Wang Z, Chen X, Xu F, Wang F, Sun R, Hu J, Song W, Yan S, Wang C Y. Dietary and lifestyle changes associated with high prevalence of hyperuricemia and gout in the Shandong coastal cities of Eastern China. J Rheumatol,2008,35(9):1859-1864.
[11]Smalley R V, Guaspari A, Haase-Statz S, Anderson S A, Cederberg D, Hohneker J A. Allopurinol:intravenous use for prevention and treatment of hyperuricemia. J Clin Oncol,2000,18(8):1758-1763.
[12]Krakoff I H, Meyer R L. Prevention of Hyperuricemia in Leukemia and Lymphoma: Use of Alopurinol, a Xanthine Oxidase Inhibitor. JAMA,1965,193:1-6.
[13]Greene M L, Fujimoto W Y, Seegmiller J E. Urinary xanthine stones--a rare complications of allopurinol therapy. N Engl J Med,1969,280(8):426-427.
[14]Wyngaarden J B. Allopurinol and xanthine nephropathy. N Engl J Med,1970, 283(7):371-372.
[15]Wortmann R L. Gout and hyperuricemia. Curr Opin Rheumatol,2002,14(3): 281-286.
[16]Yennie R H. Recognition and management of gout and hyperuricemia. JAAPA, 2003,16(3):21-24,27-28,31.
[17]Christen P, Peacock W C, Christen A E, Wacker W E. Urate oxidase in primate phylogenesis. Eur J Biochem,1970,12(1):3-5.
[18]Shnitka T K. Comparative ultrastructure of hepatic microbodies in some mammals and birds in relation to species differences in uricase activity. J Ultrastruct Res,1966,16(5):598-625.
[19]Patte C, Sakiroglu C, Ansoborlo S, Baruchel A, Plouvier E, Pacquement H, Babin-Boilletot A. Urate-oxidase in the prevention and treatment of metabolic complications in patients with B-cell lymphoma and leukemia, treated in the Societe Francaise d'Oncologie Pediatrique LMB89 protocol. Ann Oncol,2002,13(5):789-795.
[20]Cammalleri L, Malaguarnera M. Rasburicase represents a new tool for hyperuricemia in tumor lysis syndrome and in gout. Int J Med Sci,2007,4(2): 83-93.
[21]Schlesinger N, Yasothan U, Kirkpatrick P. Pegloticase. Nat Rev Drug Discov, 2011,10(1):17-18.
[22]Goldman S C, Holcenberg J S, Finklestein J Z, Hutchinson R, Kreissman S, Johnson F L, Tou C, Harvey E, Morris E, Cairo M S. A randomized comparison between rasburicase and allopurinol in children with lymphoma or leukemia at high risk for tumor lysis. Blood,2001,97(10):2998-3003.
[23]Pui C H, Mahmoud H H, Wiley J M, Woods G M, Leverger G, Camitta B, Hastings C, Blaney S M, Relling M V, Reaman G H. Recombinant urate oxidase for the prophylaxis or treatment of hyperuricemia in patients With leukemia or lymphoma. J Cl in Oncol,2001,19(3):697-704.
[24]Pui C H, Relling M V, Lascombes F, Harrison P L, Struxiano A, Mondesir J M, Ribeiro R C, Sandlund J T, Rivera G K, Evans W E, Mahmoud H H. Urate oxidase in prevention and treatment of hyperuricemia associated with lymphoid malignancies. Leukemia,1997,11(11):1813-1816.
[25]Biggers K, Scheinfeld N. Pegloticase, a polyethylene glycol conjugate of uricase for the potential intravenous treatment of gout. Curr Opin Investig Drugs,2008,9(4):422-429.
[26]Retailleau P, Colloc'h N, Vivares D, Bonnete F, Castro B, El-Hajji M, Mornon J P, Monard G, Prange T. Complexed and ligand-free high-resolution structures of urate oxidase (Uox) from Aspergillus flavus:a reassignment of the active-site binding mode. Acta Crystallogr D Biol Crystallogr,2004,60(Pt 3):453-462.
[27]Larsen K. Purification of nodule-specific uricase from soybean by arginine-sepharose affinity chromatography. Prep Biochem,1990,20(1):1-9.
[28]Suzuki H, Verma D P. Soybean Nodule-Specific Uricase (Nodulin-35) Is Expressed and Assembled into a Functional Tetrameric Holoenzyme in Escherichia coli. Plant Physiol,1991,95(2):384-389.
[29]Motojima K, Goto S. Cloning of rabbit uricase cDNA reveals a conserved carboxy-terminal tripeptide in three species. Biochim Biophys Acta,1989, 1008(1):116-118.
[30]Wu X W, Lee C C, Muzny D M, Caskey C T. Urate oxidase:primary structure and evolutionary implications. Proc Natl Acad Sci U S A,1989,86(23): 9412-9416.
[31]Ito M, Suzuki M, Takagi Y. Nucleotide sequence of cDNA and predicted amino acid sequence of rat liver uricase. Eur J Biochem,1988,173(2):459-463.
[32]Suzuki K, Sakasegawa S, Misaki H, Sugiyama M. Molecular cloning and expression of uricase gene from Arthrobacter globiformis in Escherichia coli and characterization of the gene product. J Biosci Bioeng,2004,98(3): 153-158.
[33]Yamamoto K, Kojima Y, Kikuchi T, Shigyo T, Sugihara K, Takashio M, Emi S. Nucleotide sequence of the uricase gene from Bacillus sp. TB-90. J Biochem, 1996,119(1):80-84.
[34]Nishimura H, Yoshida K, Yokota Y, Matsushima A, Inada Y. Physicochemical properties and states of sulfhydryl groups of uricase from Candida utilis. J Biochem,1982,91(1):41-48.
[35]Nguyen T, Zelechowska M, Foster V, Bergmann H, Verma D P. Primary structure of the soybean nodulin-35 gene encoding uricase II localized in the peroxisomes of uninfected cells of nodules. Proc Natl Acad Sci U S A,1985, 82(15):5040-5044.
[36]Goldman B M, Blobel G. Biogenesis of peroxisomes:intracellular site of synthesis of catalase and uricase. Proc Natl Acad Sci U S A,1978,75(10): 5066-5070.
[37]Angermuller S, Fahimi H D. Ultrastructural cytochemical localization of uricase in peroxisomes of rat liver. J Histochem Cytochem,1986,34(2): 159-165.
[38]Antonenkov V D, Grunau S, Ohlmeier S, Hiltunen J K. Peroxisomes are oxidative organelles. Antioxid Redox Signal,2010,13(4):525-537.
[39]Yeldandi A V, Yeldandi V, Kumar S, Murthy C V, Wang X D, Alvares K, Rao M S, Reddy J K. Molecular evolution of the urate oxidase-encoding gene in hominoid primates:nonsense mutations. Gene,1991,109(2):281-284.
[40]Wu X W, Muzny D M, Lee C C, Caskey C T. Two independent mutational events in the loss of urate oxidase during hominoid evolution. J Mol Evol,1992, 34(1):78-84.
[41]Ames B N, Cathcart R, Schwiers E, Hochstein P. Uric acid provides an antioxidant defense in humans against oxidant-and radical-caused aging and cancer:a hypothesis. Proc Natl Acad Sci U S A,1981,78(11):6858-6862.
[42]Cutler R G. Urate and ascorbate:their possible roles as antioxidants in determining longevity of mammalian species. Arch Gerontol Geriatr,1984, 3(4):321-348.
[43]Hooper D C, Scott G S, Zborek A, Mikheeva T, Kean R B, Koprowski H, Spitsin S V. Uric acid, a peroxynitrite scavenger, inhibits CNS inflammation, blood-CNS barrier permeability changes, and tissue damage in a mouse model of multiple sclerosis. FASEB J,2000,14(5):691-698.
[44]Mazzali M, Hughes J, Kim Y G, Jefferson J A, Kang D H, Gordon K L, Lan H Y, Kivlighn S, Johnson R J. Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension,2001,38(5): 1101-1106.
[45]Legoux R, Delpech B, Dumont X, Guillemot J C, Ramond P, Shire D, Caput D, Ferrara P, Loison G. Cloning and expression in Escherichia coli of the gene encoding Aspergillus flavus urate oxidase. J Biol Chem,1992,267(12): 8565-8570.
[46]Chu R, Lin Y, Usuda N, Rao M S, Reddy J K, Yeldandi A V. Mutational analysis of the putative copper-binding site of rat urate oxidase. Ann N Y Acad Sci, 1996,804:781-786.
[47]Miura S, Oda T, Funai T, Ito M, Okada Y, Ichiyama A. Urate oxidase is imported into peroxisomes recognizing the C-terminal SKL motif of proteins. Eur J Biochem,1994,223(1):141-146.
[48]Colloc'h N, el Hajji M, Bachet B, L'Hermite G, Schiltz M, Prange T, Castro B, Mornon J P. Crystal structure of the protein drug urate oxidase-inhibitor complex at 2.05 A resolution. Nat Struct Biol,1997,4(11):947-952.
[49]Burgisser D M, Thony B, Redweik U, Hess D, Heizmann C W, Huber R, Nar H. 6-Pyruvoyl tetrahydropterin synthase, an enzyme with a novel type of active site involving both zinc binding and an intersubunit catalytic triad motif; site-directed mutagenesis of the proposed active center, characterization of the metal binding site and modelling of substrate binding. J Mol Biol, 1995,253(2):358-369.
[50]Ploom T, Haussmann C, Hof P, Steinbacher S, Bacher A, Richardson J, Huber R. Crystal structure of 7,8-dihydroneopterin triphosphate epimerase. Structure,1999,7(5):509-516.
[51]Nar H, Huber R, Auerbach G, Fischer M, Hosl C, Ritz H, Bracher A, Meining W, Eberhardt S, Bacher A. Active site topology and reaction mechanism of GTP cyclohydrolase I. Proc Natl Acad Sci U S A,1995,92(26):12120-12125.
[52]Colloc'h N, Mornon J P, Camadro J M. Towards a new T-fold protein?:the coproporphyrinogen III oxidase sequence matches many structural features from urate oxidase. FEBS Lett,2002,526(1-3):5-10.
[53]Colloc'h N, Poupon A, Mornon J P. Sequence and structural features of the T-fold, an original tunnelling building unit. Proteins,2000,39(2): 142-154.
[54]Juan E C, Hoque M M, Shimizu S, Hossain M T, Yamamoto T, Imamura S, Suzuki K, Tsunoda M, Amano H, Sekiguchi T, Takenaka A. Structures of Arthrobacter globiformis urate oxidase-ligand complexes. Acta Crystallogr D Biol Crystallogr,2008, D64(Pt 8):815-822.
[55]Lucas K, Boland M J, Schubert K R. Uricase from soybean root nodules: purification, properties, and comparison with the enzyme from cowpea. Arch Biochem Biophys,1983,226(1):190-197.
[56]Szasz T, Watts S W. Uric acid does not affect the acetylcholine-induced relaxation of aorta from normotensive and deoxycorticosterone acetate-salt hypertensive rats. J Pharmacol Exp Ther,2010,333(3):758-763.
[57]Bayol A, Capdevielle J, Malazzi P, Buzy A, Claude Bonnet M, Colloc'h N, Mornon J P, Loyaux D, Ferrara P. Modification of a reactive cysteine explains differences between rasburicase and Uricozyme, a natural Aspergillus flavus uricase. Biotechnol Appl Biochem,2002,36(Pt 1):21-31.
[58]Hershfield M S, Kelly S J. Urate oxidase.2006.
[59]Varela-Echavarria A, Montes de Oca-Luna R, Barrera-Saldana H A. Uricase protein sequences:conserved during vertebrate evolution but absent in humans. FASEB J,1988,2(15):3092-3096.
[60]Gabison L, Prange T, Colloc'h N, El Hajji M, Castro B, Chiadmi M. Structural analysis of urate oxidase in complex with its natural substrate inhibited by cyanide:mechanistic implications. BMC Struct Biol,2008,8:32.
[61]Colloc'h N, Gabison L, Monard G, Altarsha M, Chiadmi M, Marassio G, Sopkova-de Oliveira Santos J, El Hajji M, Castro B, Abraini J H, Prange T. Oxygen pressurized X-ray crystallography:probing the dioxygen binding site in cofactorless urate oxidase and implications for its catalytic mechanism. Biophys J,2008,95(5):2415-2422.
[62]Duff A P, Trambaiolo D M, Cohen A E, Ellis P J, Juda G A, Shepard E M, Langley D B, Dooley D M, Freeman H C, Guss J M. Using xenon as a probe for dioxygen-binding sites in copper amine oxidases. J Mol Biol,2004,344(3): 599-607.
[63]Tilton R F, Jr., Kuntz I D, Jr., Petsko G A. Cavities in proteins:structure of a metmyoglobin-xenon complex solved to 1.9 A. Biochemistry,1984,23(13): 2849-2857.
[64]Wade R C, Winn P J, Schlichting I, Sudarko. A survey of active site access channels in cytochromes P450. J Inorg Biochem,2004,98(7):1175-1182.
[65]Hiromoto T, Fujiwara S, Hosokawa K, Yamaguchi H. Crystal structure of 3-hydroxybenzoate hydroxylase from Comamonas testosteroni has a large tunnel for substrate and oxygen access to the active site. J Mol Biol,2006,364(5): 878-896.
[66]Bentley R, Neuberger A. The mechanism of the action of uricase. Biochem J, 1952,52(4):694-699.
[67]Sokolic L, Modric N, Poje M. Regiochemical course of chemical and enzymic uricolysis to allantoin. A non-degradative 13C-NMR evidence. Tetrahedron Lett,1991,32:7477-7480.
[68]Kahn K, Tipton P A. Spectroscopic characterization of intermediates in the urate oxidase reaction. Biochemistry,1998,37(33):11651-11659.
[69]Frerichs-Deeken U, Ranguelova K, Kappl R, Huttermann J, Fetzner S. Dioxygenases without requirement for cofactors and their chemical model reaction:compulsory order ternary complex mechanism of 1H-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase involving general base catalysis by histidine 251 and single-electron oxidation of the substrate dianion. Biochemistry,2004,43(45):14485-14499.
[70]Sciara G, Kendrew S G, Miele A E, Marsh N G, Federici L, Malatesta F, Schimperna G, Savino C, Vallone B. The structure of ActVA-0rf6, a novel type of monooxygenase involved in actinorhodin biosynthesis. EMBO J,2003,22(2): 205-215.
[71]Fetzner S. Oxygenases without requirement for cofactors or metal ions. Appl Microbiol Biotechnol,2002,60(3):243-257.
[72]Roda A, Parisi D, Guardigli M, Zattoni A, Reschiglian P. Combined approach to the analysis of recombinant protein drugs using hollow-fiber flow field-flow fractionation, mass spectrometry, and chemiluminescence detection. Anal Chem,2006,78(4):1085-1092.
[73]Marli L M, Ubirajara P, Rodrigues F, Osvaldo N, Oliveira J, Marystela F. Immobilization of uricase in layer-by-layer films used in amperometric biosensors for uric acid J Solid State Electrochem,2007,11(1):1489-1495.
[74]Montalbini P, Aguilar M, Pineda M. Isolation and characterization of uricase from bean leaves and its comparison with uredospore enzymes. Plant Sci,1999, 147(2):139-147.
[75]Kelly S J, Delnomdedieu M, Oliverio M I, Williams L D, Saifer M G, Sherman M R, Coffman T M, Johnson G A, Hershfield M S. Diabetes insipidus in uricase-deficient mice:a model for evaluating therapy with poly(ethylene glycol)-modified uricase. J Am Soc Nephrol,2001,12(5):1001-1009.
[76]Kahn K, Tipton P A. Kinetic mechanism and cofactor content of soybean root nodule urate oxidase. Biochemistry,1997,36(16):4731-4738.
[77]Shekarriz B, Stoller M L. Uric acid nephrolithiasis:current concepts and controversies. J Urol,2002,168(4 Pt 1):1307-1314.
[78]Tokimitsu Y, Ise N, Tanaka D, Kunugi S. Uricase Model Reactions of Polylysine-Cu(Ⅱ) Complexes. Bull Chem Soc Jpn,1995,68:3277-3282.
[79]Hinberg I, O'Driscoll K F. Preparation and kinetic properties of gel entrapped urate oxidase. Biotechnol Bioeng,1975,17(10):1435-1441.
[80]Liu J, Li G, Liu H, Zhou X. Purification and properties of uricase from Candida sp. and its application in uric acid analysis in serum. Appl Biochem Biotechnol,1994,47(1):57-63.
[81]Ohe T, Watanabe Y. Purification and properties of urate oxidase from Streptomyces cyanogenus. J Biochem,1981,89(6):1769-1776.
[82]Itaya K, Yamamoto T, Fukumoto J. Studies on yeast uricase. Part I. Purification and some enzymatic properties of yeast uricase. Agric Biol Chem, 1967,31:1256-1264.
[83]Adamek V, Kralova B, Suchova M, Valentova 0, Demnerova K. Purification of microbial uricase. J Chromatogr,1989,497:268-275.
[84]Bongaerts G P, Uitzetter J, Brouns R, Vogels G D. Uricase of Bacillus fastidiosus. Properties and regulation of synthesis. Biochim Biophys Acta, 1978,527(2):348-358.
[85]Bentley K W, Truscoe R. Effect of treatment with dithiothreitol on the extraction, activity and purification of ox-kidney urate oxidase. Enzymologia,1969,37:131-152.
[86]Conley T G, Priest D G. Purification of uricase from mammalian tissue. Prep Biochem,1979,9(2):197-203.
[87]London M, Hudson P B. Uricolytic activity of purified uricase in two human beings. Science,1957,125(3254):937-938.
[88]Machida Y, Nakanishi T. Purification and properties of uricae from Enterobacter cloacae. Agric Biol Chem,1980,44:2811-2815.
[89]Nishiya Y, Hibi T, Oda J. A purification method of the diagnostic enzyme Bacillus uricase using magnetic beads and non-specific protease. Protein Expr Purif,2002,25(3):426-429.
[90]Greenberg M L, Hershfield M S. A radiochemical-high-performance liquid chromatographic assay for urate oxidase in human plasma. Anal Biochem,1989, 176(2):290-293.
[91]Haeckel R. The use of aldehyde dehydrogenase to determine H202-producing reactions. I. The determination of the uric acid concentration. J Clin Chem Clin Biochem,1976,14(3):101-107.
[92]Kageyama N. A direct colorimetric determination of uric acid in serum and urine with uricase-catalase system. Clin Chim Acta,1971,31(2):421-426.
[93]Fossati P, Prencipe L, Berti G. Use of 3,5-dichloro-2-hydroxybenzenesulfonic acid/4-aminophenazone chromogenic system in direct enzymic assay of uric acid in serum and urine. Clin Chem, 1980,26(2):227-231.
[94]Hasebe Y, Nawa K, Ujita S, Uchiyama S. Highly sensitive flow detection of uric acid based on an intermediate regeneration of uricase. Analyst,1998, 123(8):1775-1780.
[95]Tao H, Wang X, Hu Y, Ma Y, Lu Y, Hu Z. Construction of uric acid biosensor based on biomimetic titanate nanotubes. J Nanosci Nanotechnol,2010,10(2): 860-864.
[96]Roberts M J, Bentley M D, Harris J M. Chemistry for peptide and protein PEGylation. Adv Drug Deliv Rev,2002,54(4):459-476.
[97]Veronese F M, Mero A, Pasut G. Protein PEGylation, basic science and biological applications. Veronese F M. PEGylated Protein Durgs:Basic Science and Clinical Application. [C].2009.11-31.
[98]Veronese F M. Peptide and protein PEGylation:a review of problems and solutions. Biomaterials,2001,22(5):405-417.
[99]Harris J M, Chess R B. Effect of pegylation on pharmaceuticals. Nat Rev Drug Discov,2003,2(3):214-221.
[100]Zalipsky S. Chemistry of polyethylene glycol conjugates with biologically active molecules. Adv Drug Deliv Rev,1995,16:157-182.
[101]Ensor C M, Clark M A, Holtsbege F W. PEG-modified Uricase.2003.
[102]Kang J S, Deluca P P, Lee K C. Emerging PEGylated drugs. Expert Opin Emerg Drugs,2009,14(2):363-380.
[103]Kartre K. The conjugation of proteins with poly(ethylene glyclo) and other polymers. Adv Drug Deliv Rev,1993,10:91-114.
[104]Brenner B M, Hostetter T H, Humes H D. Glomerular permselectivity:barrier function based on discrimination of molecular size and charge. Am J Physiol, 1978,234(6):F455-460.
[105]Takakura Y, Fujita T, Hashida M, Sezaki H. Disposition characteristics of macromolecules in tumor-bearing mice. Pharm Res,1990,7(4):339-346.
[106]Venkatachalam M A, Rennke H G. The structural and molecular basis of glomerular filtration. Circ Res,1978,43(3):337-347.
[107]Sherman M R, Williams L D, Saifer M C P, French J A, Kwak L W, Oppenheim J J. Conjugation of high, molecular weight poly(ethylene glycol) to cytokines:granulocytemacrophage colony stimulating factors as model substrates. Harris J M, and Zalipsky S. Poly (Ethylene Glycol):Chemistry and Biological Application[C]. Washington, DC:ACS,1997.155.
[108]Molineux G. The design and development of pegfilgrastim (PEG-rmetHuG-CSF, Neulasta). Curr Pharm Des,2004,10(11):1235-1244.
[109]Veronese F M, Monfardini C, Caliceti P, Schiavon 0, Scrawen M D, Beer D. Improvement of pharmacokinetic, immunological and stability properties of asparginase by conjugation of linear and branched monomethoxy poly (ethylene glycol). J Control Release,1996,40(3):199-209.
[110]Caliceti P, Schiavon 0, Veronese F M. Immunological properties of uricase conjugated to neutral soluble polymers. Bioconjug Chem,2001,12(4): 515-522.
[111]Kompella U B, Lee V H L. Pharmacokinetics of peptide and protein drugs. Lee V H L. Peptide and Protein Drug Delivery[C].New York:Marcel Dekker, 1991.391.
[112]Conover C D, Gilbert C W, Shum K L, Shorr R G. The impact of polyethylene glycol conjugation on bovine hemoglobin's circulatory half-life and renal effects in a rabbit top-loaded transfusion model. Artif Organs,1997,21: 907-915.
[113]Caliceti P, Schiavon 0, Veronese F M. Biopharmaceutical properties of uricase conjugated to neutral and amphiphilic polymers. Bioconjug Chem, 1999,10(4):638-646.
[114]Williams D L F, CA), Hershfield, Michael S. (Durham, NC), Kelly, Susan J. (Chapel Hill, NC), Saifer, Mark G. P. (San Carlos, CA), Sherman, Merry R. (San Carlos, CA). PEG-urate oxidase conjugates and use thereof.2003, 6576235.
[115]Nishimura H, Ashihara Y, Matsushima A, Inada Y. Modification of yeast uricase with polyethylene glycol:disappearance of binding ability towards anti-uricase serum. Enzyme,1979,24(4):261-264.
[116]Nishimura H, Matsushima A, Inada Y. Improved modification of yeast uricase with polyethylene glycol, accompanied with nonimmunoreactivity towards anti-uricase serum and high enzymic activity. Enzyme,1981,26(1):49-53.
[117]Abuchowski A, Karp D, Davis F F. Reduction of plasma urate levels in the cockerel with polyethylene glycol-uricase. J Pharmacol Exp Ther,1981, 219(2):352-354.
[118]Chen R H, Abuchowski A, Van Es T, Palczuk N C, Davis F F. Properties of two urate oxidases modified by the covalent attachment of poly(ethylene glycol). Biochim Biophys Acta,1981,660(2):293-298.
[119]Tsuji J, Hirose K, Kasahara E, Naitoh M, Yamamoto I. Studies on antigenicity of the polyethylene glycol (PEG)-modified uricase. Int J Immunopharmacol, 1985,7(5):725-730.
[120]Chua C C, Greenberg M L, Viau A T, Nucci M, Brenckman W D, Jr., Hershfield M S. Use of polyethylene glycol-modified uricase (PEG-uricase) to treat hyperuricemia in a patient with non-Hodgkin lymphoma. Ann Intern Med,1988, 109(2):114-117.
[121]Yasuda Y, Fujita T, Takakura Y, Hashida M, Sezaki H. Biochemical and biopharmaceutical properties of macromolecular conjugates of uricase with dextran and polyethylene glycol. Chem Pharm Bull (Tokyo),1990,38(7): 2053-2056.
[122]Fujita T, Yasuda Y, Takakura Y, Hashida M, Sezaki H. Tissue distribution of 111In-labeled uricase conjugated with charged dextrans and polyethylene glycol. J Pharmacobiodyn,1991,14(11):623-629.
[123]Ganson N J, Kelly S J, Scarlett E, Sundy J S, Hershfield M S. Control of hyperuricemia in subjects with refractory gout, and induction of antibody against poly(ethylene glycol) (PEG), in a phase I trial of subcutaneous PEGylated urate oxidase. Arthritis Res Ther,2006,8(1):R12.
[124]Baraf H S, Matsumoto A K, Maroli A N, Waltrip R W,2nd. Resolution of gouty tophi after twelve weeks of pegloticase treatment. Arthritis Rheum,2008, 58(11):3632-3634.
[125]Young M A, Malavalli A, Winslow N, Vandegriff K D, Winslow R M. Toxicity and hemodynamic effects after single dose administration of MalPEG-hemoglobin (MP4) in rhesus monkeys. Transl Res,2007,149(6): 333-342.
[126]Savient Pharmaceuticals I. KrystexxaTM(petloticase) Injection, for intravenous infusion. http://wwwkrystexxacom/pdfs/KRYSTEXXA Prescribing_Informationpdf,2010.
[127]Bomalaski J S, Goddard D H, Grezlak D. Phase I study of uricase formulated with polyethylene glycol (Uricase-PEG 20). Arthritis Rheum,2002,46(suppl): S141.
[128]Bomalaski J S, Clark M A. Serum uric acid-lowering therapies:where are we heading in management of hyperuricemia and the potential role of uricase. Curr Rheumatol Rep,2004,6 (3):240-247.
[129]Bomalaski J S, Holtsberg F W, Ensor C M, Clark M A. Uricase formulated with polyethylene glycol (uricase-PEG 20):biochemical rationale and preclinical studies. J Rheumatol,2002,29(9):1942-1949.
[130]Ensor C M L, KY, US), Clark, Mike A. (Lexington, KY, US), Holtsberg, Frederick Wayne (Nicholasville, KY, US). PEG-modified uricase.2005, 6913915.
[131]Pui C H. Urate oxidase in the prophylaxis or treatment of hyperuricemia: the United States experience. Semin Hematol,2001,38(4 Suppl 10):13-21.
[132]Sherman M R, Saifer M G, Perez-Ruiz F. PEG-uricase in the management of treatment-resistant gout and hyperuricemia. Adv Drug Deliv Rev,2008,60(1): 59-68.
[133]Lu G, Moriyama E N. Vector NTI, a balanced all-in-one sequence analysis suite. Brief Bioinform,2004,5(4):378-388.
[134]Truszkowski R, Goldmanowna C. Uricase and its action:Distribution in various animals. Biochem J,1933,27(3):612-614.
[135]Safra N, Ling G V, Schaible R H, Bannasch D L. Exclusion of urate oxidase as a candidate gene for hyperuricosuria in the Dalmatian dog using an interbreed backcross. J Hered,2005,96(7):750-754.
[136]0da M, Satta Y, Takenaka 0, Takahata N. Loss of urate oxidase activity in hominoids and its evolutionary implications. Mol Biol Evol,2002,19(5): 640-653.
[137]Lee C C, Wu X W, Gibbs R A, Cook R G, Muzny D M, Caskey C T. Generation of cDNA probes directed by amino acid sequence:cloning of urate oxidase. Science,1988,239(4845):1288-1291.
[138]Karplus K. SAM-T08, HMM-based protein structure prediction. Nucleic Acids Res,2009,37(Web Server issue):W492-497.
[139]Lee H J, Wilson I B. Enzymic parameters:measurement of V and Km. Biochim Biophys Acta,1971,242(3):519-522.
[140]Gabison L, Chiadmi M, El Hajji M, Castro B, Colloc'h N, Prange T. Near-atomic resolution structures of urate oxidase complexed with its substrate and analogues:the protonation state of the ligand. Acta Crystallogr D Biol Crystallogr,2010,66(Pt 6):714-724.
[141]Guex N, Peitsch M C. SWISS-MODEL and the Swiss-PdbViewer:an environment for comparative protein modeling. Electrophoresis,1997,18(15): 2714-2723.
[142]Retailleau P, Colloc'h N, Vivares D, Bonnete F, Castro B, ElHajji M, Prange T. Urate oxidase from Aspergillus flavus:new crystal-packing contacts in relation to the content of the active site. Acta Crystallogr D Biol Crystallogr,2005,61 (Pt 3):218-229.
[143]Wu Y, Cao Z, Yi H, Jiang D, Mao X, Liu H, Li W. Simulation of the interaction between ScyTx and small conductance calcium-activated potassium channel by docking and MM-PBSA. Biophys J,2004,87(1):105-112.
[144]Jin L, Wu Y. Molecular mechanism of the sea anemone toxin ShK recognizing the Kvl.3 channel explored by docking and molecular dynamic simulations. J Chem Inf Model,2007,47(5):1967-1972.
[145]Allinger N L. Conformational analysis.130. MM2. A hydrocarbon force field utilizing V1 and V2 torsional terms. J Am Chem Soc,1977,99(25):8127-8134.
[146]Friesner R A, Banks J L, Murphy R B, Halgren T A, Klicic J J, Mainz D T, Repasky M P, Knoll E H, Shelley M, Perry J K, Shaw D E, Francis P, Shenkin P S. Glide:a new approach for rapid, accurate docking and scoring.1. Method and assessment of docking accuracy. J Med Chem,2004,47(7):1739-1749.
[147]Halgren T A, Murphy R B, Friesner R A, Beard H S, Frye L L, Pollard W T, Banks J L. Glide:a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. J Med Chem,2004,47(7): 1750-1759.
[148]Tsui V, Case D A. Theory and applications of the generalized Born solvation model in macromolecular simulations. Biopolymers,2000,56(4):275-291.
[149]Wang J, Cieplak P, Kollman P. How well does a restrained electrostatic potential (RESP) model perform in calculating conformational energies of organic and biological molecules? J Comput Chem,2000,21:1049-1074.
[150]Laskowski R A, MacArthur M W, Moss D S, Thornton J M. PROCHECK:a program to check the stereochemical quality of protein structures.. J App Crystallogr,1993,26:283-291.
[151]Guex N, Peitsch M C, Schwede T. Automated comparative protein structure modeling with SWISS-MODEL and Swiss-PdbViewer:a historical perspective. Electrophoresis,2009,30 Suppl 1:S162-173.
[152]Pahwa S, Kaur S, Jain R, Roy N. Structure based design of novel inhibitors for histidinol dehydrogenase from Geotrichum candidum. Bioorg Med Chem Lett, 2010,20(13):3972-3976.
[153]Ellman G L. Tissue sulfhydryl groups. Arch Biochem Biophys,1959,82(1): 70-77.
[154]Saitou N, Nei M. The neighbor-joining method:a new method for reconstructing phylogenetic trees. Mol Biol Evol,1987,4(4):406-425.
[155]Studier F W. Use of bacteriophage T7 lysozyme to improve an inducible T7 expression system. J Mol Biol,1991,219(1):37-44.
[156]Wedemeyer W J, Welker E, Narayan M, Scheraga H A. Disulfide bonds and protein folding. Biochemistry,2000,39(15):4207-4216.
[157]Imhoff R D, Power N P, Borrok M J, Tipton P A. General base catalysis in the urate oxidase reaction:evidence for a novel Thr-Lys catalytic diad. Biochemistry,2003,42(14):4094-4100.
[158]Lunelli M, Di Paolo M L, Biadene M, Calderone V, Battistutta R, Scarpa M, Rigo A, Zanotti G. Crystal structure of amine oxidase from bovine serum. J Mol Biol,2005,346(4):991-1004.
[159]Colloc'h N, Girard E, Dhaussy A C, Kahn R, Ascone I, Mezouar M, Fourme R. High pressure macromolecular crystallography:the 140-MPa crystal structure at 2.3 A resolution of urate oxidase, a 135-kDa tetrameric assembly. Biochim Biophys Acta,2006,1764(3):391-397.
[160]Poupon A, Mornon J P. Populations of hydrophobic amino acids within protein globular domains:identification of conserved "topohydrophobic" positions. Proteins,1998,33(3):329-342.
[161]Riddles P W, Blakeley R L, Zerner B. Ellman's reagent: 5,5'-dithiobis (2-nitrobenzoic acid)--a reexamination. Anal Biochem,1979, 94(1):75-81.
[162]Schrader M, Fahimi H D. The peroxisome:still a mysterious organelle. Histochem Cell Biol,2008,129(4):421-440.
[163]Rosenberg A S. Effects of protein aggregates:an immunologic perspective. AAPS J,2006,8(3):E501-507.
[164]Caliceti P, Veronese F M. Pharmacokinetic and biodistribution properties of poly (ethylene glycol)-protein conjugates. Adv Drug Deliv Rev,2003, 55(10):1261-1277.
[165]Hershfield M S. Adenosine deaminase deficiency:clinical expression, molecular basis, and therapy. Semin Hematol,1998,35(4):291-298.
[166]Pasut G, Sergi M, Veronese F M. Anti-cancer PEG-enzymes:30 years old, but still a current approach. Adv Drug Deliv Rev,2008,60(1):69-78.
[167]Parkinson C, Scarlett J A, Trainer P J. Pegvisomant in the treatment of acromegaly. Adv Drug Deliv Rev,2003,55(10):1303-1314.
[168]Freitas Dda S, Spencer P J, Vassao R C, Abrahao-Neto J. Biochemical and biopharmaceutical properties of PEGylated uricase. Int J Pharm,2010, 387(1-2):215-222.
[169]Fee C J, Van Alstine J M. Prediction of the viscosity radius and the size exclusion chromatography behavior of PEGylated proteins. Bioconjug Chem, 2004,15(6):1304-1313.
[170]Habeeb A F. Determination of free amino groups in proteins by trinitrobenzenesulfonic acid. Anal Biochem,1966,14(3):328-336.
[171]Li J, Kao W J. Synthesis of polyethylene glycol (PEG) derivatives and PEGylated-peptide biopolymer conjugates. Biomacromolecules,2003,4(4): 1055-1067.
[172]Greenfield N J. Using circular dichroism spectra to estimate protein secondary structure. Nat Protoc,2006,1 (6):2876-2890.
[173]Sundy J S, Ganson N J, Kelly S J, Scarlett E L, Rehrig C D, Huang W, Hershfield M S. Pharmacokinetics and pharmacodynamics of intravenous PEGylated recombinant mammalian urate oxidase in patients with refractory gout. Arthritis Rheum,2007,56(3):1021-1028.
[174]Rajender Reddy K, Modi M W, Pedder S. Use of peginterferon alfa-2a (40 KD) (Pegasys) for the treatment of hepatitis C. Adv Drug Deliv Rev,2002,54(4): 571-586.
[175]Bruno R, Sacchi P, Ciappina V, Zochetti C, Patruno S, Maiocchi L, Filice G. Viral dynamics and pharmacokinetics of peginterferon alpha-2a and peginterferon alpha-2b in naive patients with chronic hepatitis c:a randomized, controlled study. Antivir Ther,2004,9(4):491-497.
[176]Schiavon 0, Caliceti P, Ferruti P, Veronese F M. Therapeutic proteins:a comparison of chemical and biological properties of uricase conjugated to linear or branched poly (ethylene glycol) and poly(N-acryloylmorpholine). Farmaco,2000,55 (4):264-269.
[177]Harris M J, Kozlowski A. Poly(ethylene glycol) and related polymers monosubstituted with propionic or butanoic acids and functional derivatives thereof for biotechnical applications.1997,5672662.
[178]Wu M, Dellacherie E, Durand A, Marie E. Poly(n-butyl cyanoacrylate) nanoparticles via miniemulsion polymerization.2. PEG-based surfactants. Colloids Surf B Biointerfaces,2009,69(1):147-151.
[179]Horisberger M, Rosset J. Colloidal gold, a useful marker for transmission and scanning electron microscopy. J Histochem Cytochem,1977,25(4): 295-305.
[180]Hoiseth G, Bernard J P, Karinen R, Johnsen L, Helander A, Christophersen A S, Morland J. A pharmacokinetic study of ethyl glucuronide in blood and urine:applications to forensic toxicology. Forensic Sci Int,2007, 172(2-3):119-124.
[181]Kozlowski A, Charles S A, Harris J M. Development of PEGylated interferons for the treatment of chronic hepatitis C. BioDrugs,2001,15(7):419-429.
[182]Cheng T L, Wu P Y, Wu M F, Chern J W, Roffler S R. Accelerated clearance of polyethylene glycol-modified proteins by anti-polyethylene glycol IgM. Bioconjug Chem,1999,10(3):520-528.
[183]Ishida T, Masuda K, Ichikawa T, Ichihara M, Irimura K, Kiwada H. Accelerated clearance of a second injection of PEGylated liposomes in mice. Int J Pharm, 2003,255(1-2):167-174.
[184]Ishida T, Maeda R, Ichihara M, Irimura K, Kiwada H. Accelerated clearance of PEGylated liposomes in rats after repeated injections. J Control Release, 2003,88(1):35-42.
[185]Ishida T, Ichihara M, Wang X, Yamamoto K, Kimura J, Majima E, Kiwada H. Injection of PEGylated liposomes in rats elicits PEG-specific IgM, which is responsible for rapid elimination of a second dose of PEGylated liposomes. J Control Release,2006,112(1):15-25.
[186]Wang X, Ishida T, Kiwada H. Anti-PEG IgM elicited by injection of liposomes is involved in the enhanced blood clearance of a subsequent dose of PEGylated liposomes. J Control Release,2007,119(2):236-244.
[187]Koide H, Asai T, Hatanaka K, Akai S, Ishii T, Kenjo E, Ishida T, Kiwada H, Tsukada H, Oku N. T cell-independent B cell response is responsible for ABC phenomenon induced by repeated injection of PEGylated liposomes. Int J Pharm,2010,392(1-2):218-223.
[188]Ishihara T, Takeda M, Sakamoto H, Kimoto A, Kobayashi C, Takasaki N, Yuki K, Tanaka K, Takenaga M, Igarashi R, Maeda T, Yamakawa N, Okamoto Y, Otsuka M, Ishida T, Kiwada H, Mizushima Y, Mizushima T. Accelerated blood clearance phenomenon upon repeated injection of PEG-modified PLA-nanoparticles. Pharm Res,2009,26(10):2270-2279.
[189]Ishida T, Wang X, Shimizu T, Nawata K, Kiwada H. PEGylated liposomes elicit an anti-PEG IgM response in a T cell-independent manner. J Control Release, 2007,122(3):349-355.
[190]Ishida T, Kashima S, Kiwada H. The contribution of phagocytic activity of liver macrophages to the accelerated blood clearance (ABC) phenomenon of PEGylated liposomes in rats. J Control Release,2008,126(2):162-165.
[191]Ishida T, Harada M, Wang X Y, Ichihara M, Irimura K, Kiwada H. Accelerated blood clearance of PEGylated liposomes following preceding liposome injection:effects of lipid dose and PEG surface-density and chain length of the first-dose liposomes. J Control Release,2005,105(3):305-317.
[192]Ishida T, Kiwada H. Accelerated blood clearance (ABC) phenomenon upon repeated injection of PEGylated liposomes. Int J Pharm,2008,354(1-2): 56-62.
[193]Wang X Y, Ishida T, Ichihara M, Kiwada H. Influence of the physicochemical properties of liposomes on the accelerated blood clearance phenomenon in rats. J Control Release,2005,104(1):91-102.
[194]Efremova N T, Sheth S R, Leckband D E. Protein-induced change in poly(ethylene glycol) brushes:molecular weight and temperature difference. Langmuir,2001,17:7628-7636.
[195]Stavric B, Johnson W J, Grice H C. Uric acid nephropathy:an experimental model. Proc Soc Exp Biol Med,1969,130(2):512-516.
[196]Coderre T J, Wall P D. Ankle joint urate arthritis in rats provides a useful tool for the evaluation of analgesic and anti-arthritic agents. Pharmacol Biochem Behav,1988,29(3):461-466.
[197]Frui jtier-Polloth C. Safety assessment on polyethylene glycols (PEGs) and their derivatives as used in cosmetic products. Toxicology,2005,214(1-2): 1-38.
[198]Webster R, Didier E, Harris P, Siegel N, Stadler J, Tilbury L, Smith D. PEGylated proteins:evaluation of their safety in the absence of definitive metabolism studies. Drug Metab Dispos,2007,35(1):9-16.
[199]Keebaugh A C, Thomas J W. The evolutionary fate of the genes encoding the purine catabolic enzymes in hominoids, birds, and reptiles. Mol Biol Evol, 2010,27(6):1359-1369.
[200]Wu X, Wakamiya M, Vaishnav S, Geske R, Montgomery C, Jr., Jones P, Bradley A, Caskey C T. Hyperuricemia and urate nephropathy in urate oxidase-deficient mice. Proc Natl Acad Sci U S A,1994,91(2):742-746.
[201]Monrad S U, Killen P D, Anderson M R, Bradke A, Kaplan M J. The role of aldosterone blockade in murine lupus nephritis. Arthritis Res Ther,2008, 10(1):R5.
[202]Ekundi-Valentim E, Santos K T, Camargo E A, Denadai-Souza A, Teixeira S A, Zanoni C I, Grant A D, Wallace J, Muscara M N, Costa S K. Differing effects of exogenous and endogenous hydrogen sulphide in carrageenan-induced knee joint synovitis in the rat. Br J Pharmacol,2010,159(7):1463-1474.
[203]Edwards C K,3rd. PEGylated recombinant human soluble tumour necrosis factor receptor type I (r-Hu-sTNF-RI):novel high affinity TNF receptor designed for chronic inflammatory diseases. Ann Rheum Dis,1999,58 Suppl 1:173-81.
[204]Roth A, Mollenhauer J, Wagner A, Fuhrmann R, Straub A, Venbrocks R A, Petrow P, Brauer R, Schubert H, Ozegowski J, Peschel G, Muller P J, Kinne R W. Intra-articular injections of high-molecular-weight hyaluronic acid have biphasic effects on joint inflammation and destruction in rat antigen-induced arthritis. Arthritis Res Ther,2005,7(3):R677-686.
[205]Nolen R S. Revision process begins for AVMA euthanasia guidelines. J Am Vet Med Assoc,2009,235(3):246-247.
[206]Liebman S E, Taylor J G, Bushinsky D A. Uric acid nephrolithiasis. Curr Rheumatol Rep,2007,9(3):251-257.
[207]Schlesinger N. Management of acute and chronic gouty arthritis:present state-of-the-art. Drugs,2004,64(21):2399-2416.
[208]Edwards C K,3rd, Martin S W, Seely J, Kinstler 0, Buckel S, Bendele A M, Ellen Cosenza M, Feige U, Kohno T. Design of PEGylated soluble tumor necrosis factor receptor type I (PEG sTNF-RI) for chronic inflammatory diseases. Adv Drug Deliv Rev,2003,55(10):1315-1336.
[209]Gabay C. Cytokine inhibitors in the treatment of rheumatoid arthritis. Expert Opin Biol Ther,2002,2(2):135-149.
[210]Conover C, Lejeune L, Linberg R, Shum K, Shorr R G. Transitional vacuole formation following a bolus infusion of PEG-hemoglobin in the rat. Artif Cells Blood Substit Immobil Biotechnol,1996,24(6):599-611.
[211]Shum K L, Leon A, Viau A T, Pilon D, Nucci M, Shorr R G. The physiological and histopathological response of dogs to exchange transfusion with polyethylene glycol-modified bovine hemoglobin (PEG-Hb). Artif Cells Blood Substit Immobil Biotechnol,1996,24(6):655-683.
[212]Viau A T, Abuchowski A, Greenspan S, Davis F F. Safety evaluation of free radical scavengers PEG-catalase and PEG-superoxide dismutase. J Free Radic Biol Med,1986,2(4):283-288.
[213]Schaer D J, Schaer C A, Buehler P W, Boykins R A, Schoedon G, Alayash A I, Schaffner A. CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin. Blood,2006, 107(1):373-380.