βlactams: A new class of conformationally-rigid inhibitors of γaminobutyric acid aminotransferase

Mark Hans Hopkins*, Richard B. Silverman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

A structural similarity of several monobactams (2-4), 3-aminonocardicinic acid (6), 6-aminopenicillanic acid (7), 7-aminocephalosporanic acid (8), and 7-aminodesacetoxycephalosporanic acids (9, 10) to γaminobutyric acid (GABA) and to known inhibitors and substrates of GABA aminotransferase is described. Because of this, the above-mentioned compounds were tested as competitive inhibitors and as inactivators of pig brain GABA aminotransferase. All of the compounds were competitive inhibitors of GABA aminotransferase. On the basis of the inhibitory potency of these conformationally-rigid GABA analogues it is hypothesized that GABA is bound at the active site with its amino and carboxylate groups in a syn orientation. None of the compounds inactivates GABA aminotransferase. These βlactam analogues represent the first examples of a new class of inhibitors of GABA aminotransferase.

Original languageEnglish (US)
Pages (from-to)125-129
Number of pages5
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume6
Issue number2
DOIs
StatePublished - 1992

Keywords

  • Cephalosporins
  • Monobactams
  • Penicillins
  • βLactams
  • γaminobutyric acid
  • γaminobutyric acid aminotransferase

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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