4-Amino-3-alkylbutanoic acids as substrates for γ-aminobutyric acid aminotransferase

A variety of alkyl-substituted 4-aminobutanoic acid derivatives, including a homologous series of 3-alkyl-4-aminobutanoic acid analogues, 4-methyl isomer analogues, the 3,3-dimethyl analogue, and (E)-4-amino-3-methyl-2-butenoic acid, were synthesized and tested as alternate substrates for purified γ-aminobutyric acid aminotransferase from pig brain. All of the compounds were substrates, but their activities diminished as the size and bulk of the 3-alkyl substituent increased. Several differences were observed between the alkyl-substituted analogues and the corresponding aryl-substituted compounds previously reported (Silverman, R.B., Invergo, B.J., and Levy, M.A. (1987) J. Biol. Chem. 262, 3192-3195). These findings will be important in future designs of inhibitors of γ-aminobutyric acid aminotransferase.