加巴喷丁对γ-氨基丁酸转氨酶失活产物的分离与鉴定

Isolation and characterization of the product of inactivation of gamma-aminobutyric acid aminotransferase by gabaculine.

作者信息

Fu M, Silverman R B

机构信息

Department of Chemistry, Northwestern University, Evanston, IL 60208-3113, USA.

出版信息

Bioorg Med Chem. 1999 Aug;7(8):1581-90. doi: 10.1016/s0968-0896(99)00081-4.

DOI:10.1016/s0968-0896(99)00081-4

PMID:10482450

Abstract

Gabaculine (5-amino-1,3-cyclohexadienylcarboxylic acid, 1), a naturally occurring neurotoxin isolated from Streptomyces toyocaenis, has been shown to be a mechanism-based inactivator of gamma-aminobutyric acid aminotransferase (GABA-AT) (Rando, R. R. Biochemistry 1977, 16, 4604). Inactivation results from reaction of gabaculine with the pyridoxal 5'-phosphate (PLP) cofactor. Two HPLC systems for isolating this inactivator-PLP adduct are described as well as a detailed characterization of the adduct, including the ultraviolet-visible spectrum, electrospray mass spectra, and NMR spectrum. The same spectral characterization of the chemically synthesized gabaculine-PLP adduct is also reported.

摘要

加巴喷丁（5-氨基-1,3-环己二烯基羧酸，1）是从丰田链霉菌中分离出的一种天然存在的神经毒素，已被证明是γ-氨基丁酸转氨酶（GABA-AT）的基于机制的失活剂（兰多，R.R.《生物化学》1977年，16卷，4604页）。失活是加巴喷丁与磷酸吡哆醛（PLP）辅因子反应的结果。描述了两种用于分离这种失活剂-PLP加合物的高效液相色谱系统，以及该加合物的详细表征，包括紫外可见光谱、电喷雾质谱和核磁共振谱。还报道了化学合成的加巴喷丁-PLP加合物的相同光谱表征。