title: Synthesis and evaluation of novel aromatic substrates and competitive inhibitors of GABA aminotransferase.
abstract: The design, synthesis, and evaluation of novel gamma-aminobutyric acid aminotransferase (GABA-AT) inhibitors and inactivators can lead to the discovery of new GABA-related therapeutics. To this end, a series of aromatic amino acid compounds was synthesized to aid in the design of new inhibitors and inactivators of GABA-AT. All compounds were tested as competitive inhibitors of GABA-AT. The amino acids with benzylic amines were also tested as substrates for GABA-AT. It was found that these compounds were all poor competitive inhibitors of GABA-AT, but some were substrates of the enzyme, suggesting their utility as scaffolds for potential GABA-AT mechanism-based inactivators. Computer modeling was used to rationalize the substrate activity of the various compounds.
authors.affiliation: Department of Chemistry, Northwestern University, Evanston, IL 60208-3113, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Clift
authors.forename: Richard B
authors.initials: RB
authors.lastname: Silverman
mesh_terms: D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D001667:Binding, Competitive; D003198:Computer Simulation; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006841:Hydrocarbons, Aromatic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure
chemical_list: D004791:Enzyme Inhibitors; D006841:Hydrocarbons, Aromatic; D000612:4-Aminobutyrate Transaminase