Bivalent transition-state analogue inhibitors of human glyoxalase I.
Bivalent transition-state analogue inhibitors of human glyoxalase I.
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DOI：
10.1021/ol035917s
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发表时间：
2003-11
期刊：
影响因子：
5.2
通讯作者：
Zhe-Bin Zheng;D. J. Creighton
中科院分区：
文献类型：
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作者：
Zhe-Bin Zheng;D. J. Creighton
通过将两个过渡态类似物S-（N-4-氯苯基-N-羟基氨基甲酰基）谷胱甘肽（CHG）分子的γ-谷氨酰基-NH（2）基团与不同长度的聚-β-丙氨酰系链[CHG（beta-ala）n]（2）辛二酸二酰胺（n = 1-7）交联，产生了一类新的同二聚体人谷胱甘肽酶I竞争性抑制剂。这种抗肿瘤靶酶的最强抑制剂可能同时结合每个亚基上的活性位点，得到小至0.96 nM的K（i）值（n = 6）。[结构：见正文]
A new class of competitive inhibitors of homodimeric human glyoxalase I has been created by cross-linking two molecules of the transition-state analogue S-(N-4-chlorophenyl-N-hydroxycarbamoyl)glutathione (CHG) through their gamma-glutamyl-NH(2) groups with poly-beta-alanyl tethers of differing length: [CHG(beta-ala)n](2) suberate diamide (n = 1-7). The strongest inhibitors of this antitumor target enzyme likely bind simultaneously to the active site on each subunit to give K(i) values as small as 0.96 nM (n = 6). [structure: see text]