5-C代马来酰亚胺用于半胱氨酸生物共轭标记
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- 英文论文题名：5-Methylene Maleimides for Cysteine Bioconjugation
- 论文作者：周小平 ; 章映茜 ; 席真 ; 周传政
- 英文论文作者：Xiaoping Zhou ; Yingqian Zhang ; Zhen Xi ; Chuanzheng Zhou ; State Key Laboratory of Elemento-Organic Chemistry ; Department of Chemical Biology ; Nankai University ; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin)
- 年：2016
- 作者机构：元素有机化学国家重点实验室,化学生物学系,南开大学;天津化学化工协同创新中心;
- 论文关键词：生物共轭 ; 半胱氨酸 ; 马来酰亚胺
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十八分会：化学生物学
- 语种：中文
- 分类号：O626.13
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十八分会 ; 化学生物学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：2
- 文件大小：285k
- 原文格式：D
- 会议级别：全国
摘要
马来酰亚胺是一种常用的半胱氨酸生物共轭标记分子~1,但它本身不稳定~(2,3),而且共轭产物复杂多样、易水解。我们发现5-C代马来酰亚胺是一个很好的替代物~4。含有伯氨的小分子、生物大分子、固相载体等可以通过一步反应高效转化为5-C代马来酰亚胺。5-C代马来酰亚胺在酸性和碱性条件下都稳定,与巯基发生快速Michael加成,且不产生新的手性中心。在pH6.0-9.5范围内,5-C代马来酰亚胺对多肽和蛋白质中半胱氨酸的生物共轭有高度选择性,共轭产物在酸性、中性、碱性、氧化和还原条件下都较马来酰亚胺对应产物更为稳定。因此,相对于马来酰亚胺而言,5-C代马来酰亚胺是一个易于制备、更稳定、有更高选择性的半光氨酸生物共轭标记分子,在抗体偶联药物的制备、生物大分子的固定及交联等领域有潜在的应用价值。
Maleimides are widely used for cysteine bioconjugation.However,their drawbacks are obvious:they are not stable;bioconjugation is not specific to cysteine;conjugates are liable to hydrolysis.Here we report 5-methylene maleimides as better alternatives to maleimides.Any primary amine contained small molecules,biomacromolecules,solid supports can be efficiently transformed to 5-methylene maleimides via one-step coupling.The obtained 5-methylene maleimides are stable under not only acid but basic conditions,react rapidly with thiols without generating any new chiral center.In the range of pH 6.0- 9.5,5-methylene maleimides react specifically with cysteines.The obtained conjugates are more stable in acidic,basic,oxidation or reduction buffer than maleimide counterparts.Hence,comparison to maleimides,5-methylene maleimides are easier to prepare,more stable,more specific cysteine bioconjugation molecules.They may have potential applications in many areas such as antibody-drug preparation,biomolecule immobilization and crosslink.
Maleimides are widely used for cysteine bioconjugation.However,their drawbacks are obvious:they are not stable;bioconjugation is not specific to cysteine;conjugates are liable to hydrolysis.Here we report 5-methylene maleimides as better alternatives to maleimides.Any primary amine contained small molecules,biomacromolecules,solid supports can be efficiently transformed to 5-methylene maleimides via one-step coupling.The obtained 5-methylene maleimides are stable under not only acid but basic conditions,react rapidly with thiols without generating any new chiral center.In the range of pH 6.0- 9.5,5-methylene maleimides react specifically with cysteines.The obtained conjugates are more stable in acidic,basic,oxidation or reduction buffer than maleimide counterparts.Hence,comparison to maleimides,5-methylene maleimides are easier to prepare,more stable,more specific cysteine bioconjugation molecules.They may have potential applications in many areas such as antibody-drug preparation,biomolecule immobilization and crosslink.
引文
[1]Boutureira,O.;Bernardes,G.J.L.Chem.Rev.2015,115:2174.
[2]Fontaine,S.D.;Reid,R.;Robinson,L.;Ashley,G.W.;Santi,D.V.Bioconjugate Chem.2015,26:145.
[3]Kalia,D.;Malekar,P.V.;Parthasarathy,M.Angew.Chem.Int.Ed.Engl.2016,55:1432.
[4]Zhou,X.;Zhang,Y.;Xi,Z.;Zhou,C.Manuscript under preparation.
[2]Fontaine,S.D.;Reid,R.;Robinson,L.;Ashley,G.W.;Santi,D.V.Bioconjugate Chem.2015,26:145.
[3]Kalia,D.;Malekar,P.V.;Parthasarathy,M.Angew.Chem.Int.Ed.Engl.2016,55:1432.
[4]Zhou,X.;Zhang,Y.;Xi,Z.;Zhou,C.Manuscript under preparation.