| Abstract: | Crayfish glutamic acid decarboxylase (GAD) is inhibited by some aliphatic carboxylic acid analogs of glutamate and gamma-amino-n-butyric acid (GABA). Variations in the length of the carbon skeleton, substitution of a keto for a methylene group, replacement of the carboxyl group or attachment of a bulky basic moiety to the amino terminus of GABA all lead to a drastic reduction in its inhibitory activity. Substitution of a methyl group for the amino group of GABA is a permissible alteration which does not reduce the inhibitory potency. Some structural analogs of glutamate are inhibitory also, particularly if they possess a comparable carbon skeleton and a keto group in the alpha position or a sulfhydryl group. Most of the sulfhydryl analogs are significantly more potent as inhibitors than the corresponding compounds in which the SH group is replaced by an H atom. |
