N-β-苯丙酰基-L-酪氨酸及其衍生物对非洲大蜗牛（Achatina fulica Férussac）一种可识别的巨型神经元抑制作用的构效关系

Structure-activity relationships of N-beta-phenylpropionyl-L-tyrosine and its derivatives on the inhibition of an identifiable giant neurone of an African giant snail (Achatina fulica Férussac).

作者信息

Ariyoshi Y, Takeuchi H

出版信息

Br J Pharmacol. 1982 Dec;77(4):631-9. doi: 10.1111/j.1476-5381.1982.tb09341.x.

DOI:10.1111/j.1476-5381.1982.tb09341.x

PMID:7150871

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2044684/

Abstract

1 Inhibitory effects of N-beta-phenylpropionyl-L-tyrosine, N-beta-phenylpropionyl-L-tryptophan and their derivatives on an identifiable giant neurone, TAN (tonically autoactive neurone) of an African giant snail (Achatina fulica Férussac) were examined in an attempt to elucidate which structural features are necessary to produce the effect. 2 Of the compounds examined, N-beta-cyclohexylpropionyl-L-tyrosine showed the strongest effect. Its critical concentration (c.c.) was 3 X 10(-8)-10(-7)M, about ten times lower than that of N-beta-phenylpropionyl-L-tyrosine (c.c., 3 X 10(-7)-10(-6)M). N-beta-cyclohexylpropionyl-L-tryptophan (c.c., 10(-6)M) had an effect almost similar to that of N-beta-phenylpropionyl-L-tryptophan (c.c., 10(-6)M). 3 N-beta-Phenylpropionyl-N-methyl-L-tyrosine had no effect at a high concentration. 4 Effects of N-beta-phenylpropionyl-L-tyrosine amide (c.c., 3 X 10(-7)-10(-6)M) and N-beta-phenylpropionyl-L-tryptophan amide (c.c., 10(-6)M) were very similar to those of N-beta-phenylpropionyl-L-tyrosine and N-beta-phenylpropionyl-L-tryptophan respectively. 5 N-beta-Phenylpropionyl-p-amino-L-phenylalanine (c.c., 3 X 10(-5)-10(-4)M) and N-beta-phenylpropionyl-p-chloro-L-phenylalanine (c.c., 10(-4)M) had only a weak effect. 6 It is proposed that the structural features producing the effect are as follows: the active compound has a phenyl or a cyclohexyl group (hydrophobic binding group), after a suitable distance a peptide bond (proton donor and proton acceptor), adjacently a carbonyl group (proton acceptor), and a phenolic hydroxyl or an indolyl imino group (proton donor) in the molecule.

摘要

1 研究了N-β-苯丙酰基-L-酪氨酸、N-β-苯丙酰基-L-色氨酸及其衍生物对非洲大蜗牛（Achatina fulica Férussac）中一种可识别的巨型神经元TAN（紧张性自发放电神经元）的抑制作用，以试图阐明产生该效应所需的结构特征。2 在所研究的化合物中，N-β-环己基丙酰基-L-酪氨酸显示出最强的效应。其临界浓度（c.c.）为3×10⁻⁸ - 10⁻⁷M，比N-β-苯丙酰基-L-酪氨酸的临界浓度（c.c.，3×10⁻⁷ - 10⁻⁶M）低约十倍。N-β-环己基丙酰基-L-色氨酸（c.c.，10⁻⁶M）的效应几乎与N-β-苯丙酰基-L-色氨酸（c.c.，10⁻⁶M）的效应相似。3 N-β-苯丙酰基-N-甲基-L-酪氨酸在高浓度时无作用。4 N-β-苯丙酰基-L-酪氨酸酰胺（c.c.，3×10⁻⁷ - 10⁻⁶M）和N-β-苯丙酰基-L-色氨酸酰胺（c.c.，10⁻⁶M）的效应分别与N-β-苯丙酰基-L-酪氨酸和N-β-苯丙酰基-L-色氨酸的效应非常相似。5 N-β-苯丙酰基-p-氨基-L-苯丙氨酸（c.c.，3×10⁻⁵ - 10⁻⁴M）和N-β-苯丙酰基-p-氯-L-苯丙氨酸（c.c.，10⁻⁴M）只有微弱的效应。6 提出产生该效应的结构特征如下：活性化合物分子中具有一个苯基或环己基（疏水结合基团），在适当距离后有一个肽键（质子供体和质子受体），相邻有一个羰基（质子受体），以及一个酚羟基或吲哚基亚氨基（质子供体）。