Synthesis and evaluation of new 脙脙脙脙-borono-脙脙脙脙-amino acids as rat liver arginase inhibitors
- 作者：Busnel ; Olivier ; Carreaux ; Fran脙脙ois ; Carboni ; Bertrand ; Pethe ; Stephanie ; Goff ; Sandrine Vadon-Le ; et. al.
- 关键词：Rat liver arginase ; Inhibitors ; 脙脙脙脙-Amino acids ; Boronic acids
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2005
- 期刊代码：9_09680896
- 类别：ch
- 出版时间：April 1, 2005
- 卷：13
- 期：7
- 页码：2373-2379
- 文件大小：167 K
摘要
Recent studies have demonstrated that arginase plays important roles in pathologies such as asthma or erectile dysfunctions. We have synthesized new 脧脧-borono-脧脧-amino acids that are analogues of the previously known arginase inhibitors S-(2-boronoethyl)-l-cysteine (BEC) and 2-amino-6-boronohexanoic acid (ABH) and evaluated them as inhibitors of purified rat liver arginase (RLA). In addition to the distance between the B(OH)2 and the 脧脧-amino acid functions, the position of the sulfur atom in the side chain also appears as a key determinant for the interaction with the active site of RLA. Furthermore, substitution of the alkyl side chain of BEC by methyl groups and conformational restriction of ABH by incorporation of its side chain in a phenyl ring led to inactive compounds. These results suggest that subtle interactions govern the affinity of inhibitors for the active site of RLA.