4-Amino-3-alkylbutanoic acids as substrates for gamma-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 gamma-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 gamma-aminobutyric acid aminotransferase.
Andruszkiewicz
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Department of Chemistry, Northwestern University, Evanston, Illinois 60208-3113.
Silverman
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RB
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism*; D000478:Alkylation; D000613:Aminobutyrates / Q000138:chemical synthesis / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology; D007202:Indicators and Reagents; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D009904:Optical Rotation; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013552:Swine
D000613:Aminobutyrates; D007202:Indicators and Reagents; D000612:4-Aminobutyrate Transaminase