The discovery and structure-activity relationships of indole-based inhibitors of glutamate carboxypeptidase II

Brian Grella, Jessica Adams, James F. Berry, Greg Delahanty, Dana V. Ferraris, Pavel Majer, Chiyou Ni, Krupa Shukla, Scott A. Shuler, Barbara S. Slusher, Marigo Stathis, Takashi Tsukamoto

Research output: Contribution to journalArticlepeer-review

Abstract

A series of N-substituted 3-(2-mercaptoethyl)-1H-indole-2-carboxylic acids were synthesized as inhibitors of glutamate carboxypeptidase II (GCPII). Those containing carboxybenzyl or carboxyphenyl groups at the N-position exhibited potent inhibitory activity against GCPII. These indole-based compounds represent the first example of achiral GCPII inhibitors and demonstrate greater tolerance of the GCPII active site for ligands with significant structural difference from the endogenous substrate, N-acetyl-aspartylglutamate.

Original languageEnglish (US)
Pages (from-to)7222-7225
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume20
Issue number24
DOIs
StatePublished - Dec 15 2010

Keywords

  • Glutamate carboxypeptidase II
  • Indole
  • Inhibitor
  • Metallopeptidase
  • Thiol

ASJC Scopus subject areas

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

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