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 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 1998

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Peptidomimetics
rap1 GTP-Binding Proteins
Cells
Dipeptides
G1 Phase
Cell Division
Cell Cycle
Proteins
Derivatives
Processing
geranylgeranyltransferase type-I
In Vitro Techniques
GGTI 298

ASJC Scopus subject areas

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

Cite this

Selective inhibition of type-I geranylgeranyltransferase in vitro and in whole cells by CAAL peptidomimetics. / Qian, Yimin; Vogt, Andreas; Vasudevan, Anil; Sebti, Saïd M.; Hamilton, Andrew.

In: Bioorganic and Medicinal Chemistry, Vol. 6, No. 3, 03.1998, p. 293-299.

Research output: Contribution to journalArticle

Qian, Yimin ; Vogt, Andreas ; Vasudevan, Anil ; Sebti, Saïd M. ; Hamilton, Andrew. / Selective inhibition of type-I geranylgeranyltransferase in vitro and in whole cells by CAAL peptidomimetics. In: Bioorganic and Medicinal Chemistry. 1998 ; Vol. 6, No. 3. pp. 293-299.
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