ω-氨基酸的ω-氟甲基类似物作为4-氨基丁酸：2-氧代戊二酸转氨酶的不可逆抑制剂

omega-Fluoromethyl analogues of omega-amino acids as irreversible inhibitors of 4-aminobutyrate:2-oxoglutarate aminotransferase.

作者信息

Bey P, Jung M J, Gerhart F, Schirlin D, Van Dorsselaer V, Casara P

出版信息

J Neurochem. 1981 Nov;37(5):1341-4. doi: 10.1111/j.1471-4159.1981.tb04688.x.

DOI:10.1111/j.1471-4159.1981.tb04688.x

Abstract

omega-Monofluoromethyl and omega-difluoromethyl analogues of the known substrates of GABA-T, beta-alanine, gamma-aminobutyric acid, and 5-aminopentanoic acid, are time-dependent inhibitors of purified 4-aminobutyrate: 2-oxoglutarate aminotransferase (GABA-T). The inhibitory activity decreases with increasing chain length. In vitro, inhibitory activity decreases with increasing fluorine substitution of the methyl group. In vivo, beta-difluoromethyl-beta-alanine and 2,4-difluoro-3-aminobutyric acid are the most potent GABA-T inhibitors ever reported. Trifluoromethyl derivatives are devoid of GABA-T inhibitory activity in vitro or in vivo.

摘要

γ-氨基丁酸转氨酶（GABA-T）已知底物β-丙氨酸、γ-氨基丁酸和5-氨基戊酸的ω-单氟甲基和ω-二氟甲基类似物是纯化的4-氨基丁酸：2-氧代戊二酸转氨酶（GABA-T）的时间依赖性抑制剂。抑制活性随链长增加而降低。在体外，抑制活性随甲基氟取代的增加而降低。在体内，β-二氟甲基-β-丙氨酸和2,4-二氟-3-氨基丁酸是有史以来报道的最有效的GABA-T抑制剂。三氟甲基衍生物在体外或体内均无GABA-T抑制活性。