5-取代间苯二甲酸的合成及与牛肝谷氨酸脱氢酶的竞争性抑制研究

Synthesis of 5-substituted isophthalic acids and competitive inhibition studies with bovine liver glutamate dehydrogenase.

作者信息

Boots S G, Franklin M A, Dunlavey B, Costello J, Lipsitz C, Boots M R, Rogers K S

出版信息

Proc Soc Exp Biol Med. 1976 Feb;151(2):316-20. doi: 10.3181/00379727-151-39200.

Abstract

Isophthalic acid, 5-carboxy-, 5-hydroxy-, 5-methoxy-, 5-fluoro-, 5-bromo-, 5-cyano-, and 5-methylisophthalic acid were inhibitors competitive with L-glutamate for bovine liver glutamate dehydrogenase. The extent of inhibition by the derived compounds was not much greater than that obtained with the parent compound, isophthalic acid. A plot of pKi versus pH showed the presence of an ionizable group (pKa 7.4-7.8) at the enzyme active site which interacted with the substitutent at the 5 position of the substituted isophthalates.

摘要

间苯二甲酸、5-羧基间苯二甲酸、5-羟基间苯二甲酸、5-甲氧基间苯二甲酸、5-氟间苯二甲酸、5-溴间苯二甲酸、5-氰基间苯二甲酸和5-甲基间苯二甲酸是与L-谷氨酸竞争牛肝谷氨酸脱氢酶的抑制剂。衍生化合物的抑制程度并不比母体化合物间苯二甲酸的抑制程度大多少。pKi对pH的作图表明，在酶活性位点存在一个可电离基团（pKa 7.4 - 7.8），它与取代间苯二甲酸酯5位上的取代基相互作用。