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ID: ALA1144833

Journal: Bioorg Med Chem Lett

Title: Synthesis and evaluation of novel aromatic substrates and competitive inhibitors of GABA aminotransferase.

Authors: Clift MD, Silverman RB.

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.

CiteXplore: 17988865

DOI: 10.1016/j.bmcl.2007.10.060