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.
authors.affiliation: Department of Chemistry, University of Pittsburgh, PA 15260, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Qian
authors.forename: A
authors.initials: A
authors.lastname: Vogt
authors.forename: A
authors.initials: A
authors.lastname: Vasudevan
authors.forename: S M
authors.initials: SM
authors.lastname: Sebti
authors.forename: A D
authors.initials: AD
authors.lastname: Hamilton
mesh_terms: D016475:3T3 Cells / Q000187:drug effects / Q000201:enzymology; D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D051379:Mice; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D017368:Protein Prenylation; D013329:Structure-Activity Relationship; D020668:rap GTP-Binding Proteins
chemical_list: D004791:Enzyme Inhibitors; D009842:Oligopeptides; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D019204:GTP-Binding Proteins; D020668:rap GTP-Binding Proteins