Selective inhibition of type-I geranylgeranyltransferase in vitro and in whole cells by CAAL peptidomimetics

Yimin Qian, Andreas Vogt, Anil Vasudevan, Saïd M. Sebti, Andrew D. Hamilton

Research output: Contribution to journalArticle

Abstract

In this paper we describe the synthesis of a family of CAAL peptidomimetics as GGTase-I inhibitors. These inhibitors lack the central dipeptide AA in the key CAAL carboxy terminal sequence of geranylgeranylated proteins and are more selective for GGTase-I over FTase. In whole cells, these compounds are very potent inhibitors of the processing of the geranylgeranylated protein Rap1A without affecting the farnesylated protein H-Ras. One derivative, GGTI-298, inhibited cell division by blocking cells in the G1 phase of the cell cycle.

Original languageEnglish (US)
Pages (from-to)293-299
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume6
Issue number3
DOIs
StatePublished - Mar 1 1998

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ASJC Scopus subject areas

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

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