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

doi:10.1016/S0968-0896(97)10040-2

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

Chemistry

Research output: Contribution to journal › Article › peer-review

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 language	English (US)
Pages (from-to)	293-299
Number of pages	7
Journal	Bioorganic and Medicinal Chemistry
Volume	6
Issue number	3
DOIs	https://doi.org/10.1016/S0968-0896(97)10040-2
State	Published - Mar 1998

ASJC Scopus subject areas

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

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10.1016/S0968-0896(97)10040-2

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title = "Selective inhibition of type-I geranylgeranyltransferase in vitro and in whole cells by CAAL peptidomimetics",

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.",

author = "Yimin Qian and Andreas Vogt and Anil Vasudevan and Sebti, {Sa{\"i}d M.} and Hamilton, {Andrew D.}",

note = "Funding Information: We thank the National Institutes of Health (CA 67771) for financial support of this work. ",

year = "1998",

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doi = "10.1016/S0968-0896(97)10040-2",

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T1 - Selective inhibition of type-I geranylgeranyltransferase in vitro and in whole cells by CAAL peptidomimetics

AU - Qian, Yimin

AU - Vogt, Andreas

AU - Vasudevan, Anil

AU - Sebti, Saïd M.

AU - Hamilton, Andrew D.

N1 - Funding Information: We thank the National Institutes of Health (CA 67771) for financial support of this work.

PY - 1998/3

Y1 - 1998/3

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

Abstract

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