IDENTIFICATION OF A 2ND GLYCINE-LIKE FRAGMENT ON THE STRYCHNINE MOLECULE

被引:11
作者
APRISON, MH
GALVEZRUANO, E
LIPKOWITZ, KB
机构
[1] INDIANA UNIV,SCH MED,DEPT PSYCHIAT,INDIANAPOLIS,IN 46202
[2] INDIANA UNIV,SCH MED,DEPT BIOCHEM,INDIANAPOLIS,IN 46202
[3] INDIANA UNIV PURDUE UNIV,DEPT CHEM,INDIANAPOLIS,IN 46205
关键词
GLYCINE; STRYCHNINE; MOLECULAR MODELING; INHIBITORY NEUROTRANSMITTER;
D O I
10.1002/jnr.490400314
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Strychnine is a complex molecule that inhibits the physiological actions of glycine, an important inhibitory neurotransmitter in the spinal cord, brain stem, and other areas of many vertebrates. Since 1987, we have employed atomistic molecular modeling tools to find an explanation at the molecular level for how this antagonism works. We have located a second glycine-like fragment in the strychnine molecule that, when compared to glycine in a three pair atom analysis, provides an excellent topological and electronic charge congruence. The topological congruence in the second glycine-like fragment is much better than with the first fragment reported in 1987 when using a truncated strychnine molecule in the quantum mechanical analysis. A fourth negative atom, a characteristic of antagonists which we reported earlier (Aprison and Lipkowitz: J Neurosci Res 30:442-446, 1991; Aprison and Lipkowitz: J Neurosci Res 31:166-174, 1992) was found in strychnine. This result follows the pattern reported recently for the three weak glycine antagonists N,N-dimethylmuscimol, N-methyl-THIP, and iso-THAO, a bicyclic 5-isoxazolol zwitterion. (C) 1995 Wiley-Liss, Inc.
引用
收藏
页码:396 / 400
页数:5
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