Optically active 2-benzyl-3-methanesulfinylpropanoic acid: Synthesis and evaluation as inhibitors for carboxypeptidase A.
Optically active 2-benzyl-3-methanesulfinylpropanoic acid: Synthesis and evaluation as inhibitors for carboxypeptidase A.
复制标题
光学活性 2-苄基-3-甲亚磺酰基丙酸：作为羧肽酶 A 抑制剂的合成和评价。
DOI：
10.1016/s0968-0896(03)00481-4
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发表时间：
2003
影响因子：
3.5
通讯作者：
D. H. Kim
中科院分区：
文献类型：
--
作者：
Jing;G. Tian;D. H. Kim
合成了2-苄基-3-甲烷亚磺酰基丙酸的所有四种可能的立体异构体，并将其作为羧肽酶A的抑制剂进行了评价，发现具有（2S，4S）-构型的异构体是最有效的，其次是（2 R，4S）-和（2S，4 R）-构型的异构体。该抑制剂的异构体与酶结合时的立体化学偏好表明，该抑制剂中的亚砜氧不能与活性中心锌离子连接，但可以与Arg-127的胍基形成氢键，就像酶的寡肽底物的易断裂的肽键的羰基氧一样。因此可以推断，亚砜部分可以用作甲酰胺部分的电子等排体。
All four possible stereomers of 2-benzyl-3-methanesulfinylpropanoic acid were synthesized and evaluated as inhibitors for carboxypeptidase A to find that the isomer having the (2S,4S)-configuration is most potent followed by isomers of (2R,4S)- and (2S,4R)-configurations. The stereochemical preferences shown by the isomers of the inhibitor in binding to the enzyme suggest that the sulfoxide oxygen in the inhibitor fails to ligate the active site zinc ion but may form a hydrogen bond with the guanidinium moiety of Arg-127 like the carbonyl oxygen of scissile peptide bond of oligopeptide substrate of the enzyme does. It may thus be inferred that a sulfoxide moiety may serve as an isosterer of a carboxamide moiety.