Synthesis and evaluation of novel aromatic substrates and competitive inhibitors of GABA aminotransferase

Michael D. Clift, Richard B. Silverman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

The design, synthesis, and evaluation of novel γ-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.

Original languageEnglish (US)
Pages (from-to)3122-3125
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number10
DOIs
StatePublished - May 15 2008

Keywords

  • Aromatic amino acid
  • Computer modeling
  • GABA-AT
  • Inhibitor
  • Substrate of GABA-AT
  • γ-Aminobutyric acid
  • γ-Aminobutyric acid aminotransferase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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