4-（氧代烷基）取代的GABA类似物作为GABA转氨酶的失活剂和底物。

4-(Oxoalkyl)-substituted GABA analogues as inactivators and substrates of GABA aminotransferase.

作者信息

Burke J R, Silverman R B

机构信息

Department of Chemistry, Northwestern University, Evanston, Illinois 60208-3113.

出版信息

J Enzyme Inhib. 1991;5(3):199-205. doi: 10.3109/14756369109080058.

DOI:10.3109/14756369109080058

PMID:1669447

Abstract

On the basis of the mechanism of inactivation of gamma-aminobutyric acid (GABA) aminotransferase by gamma-ethynyl GABA that was reported recently (Burke and Silverman, manuscript submitted), three 4-(oxoalkyl)-substituted GABA analogues, 4-amino-5-oxohexanoic acid (7), 4-amino-5-oxopentanoic acid (8), and 4-amino-6-oxohexanoic acid (9) were synthesized and tested as inactivators. Only 8 was an inactivator of the enzyme. A mechanism for the inactivation by 8 is proposed as well as rationalizations for the lack of inactivation by 7 and 9.

摘要

基于最近报道的γ-乙炔基 GABA 对γ-氨基丁酸（GABA）转氨酶的失活机制（Burke 和 Silverman，稿件待提交），合成了三种 4-(氧代烷基)取代的 GABA 类似物，即 4-氨基-5-氧代己酸（7）、4-氨基-5-氧代戊酸（8）和 4-氨基-6-氧代己酸（9），并将其作为失活剂进行测试。只有 8 是该酶的失活剂。本文提出了 8 失活的机制，以及对 7 和 9 缺乏失活作用的解释。