title: Synthesis and biological activity of semipeptoid farnesyltransferase inhibitors.
abstract: Semipeptoids derived from the Ras farnesyl transferase inhibitor, CVFM, were synthesized by the Simultaneous Multiple Analogue Peptide Synthesis methodology. The semipeptoids were screened for their in vitro inhibition potency towards farnesyl transferase and geranylgeranyl transferase. Structure-activity relationship studies led to a potent and selective inhibitor, HR-11, which blocks Ras farnesylation in vitro with an IC50 of 1.2 nM. The cell permeable methyl ester derivative of HR-11, HR-12, inhibits Ras farnesylation in intact cells with an IC50 of 10 microM and with no detectable inhibition of Rap1A/K-rev geranyl-geranylation.
authors.affiliation: Department of Biological, Institute of Life Sciences, Hebrew University of Jerusalem, Israel.
authors.forename: H
authors.initials: H
authors.lastname: Reuveni
authors.forename: A
authors.initials: A
authors.lastname: Gitler
authors.forename: E
authors.initials: E
authors.lastname: Poradosu
authors.forename: C
authors.initials: C
authors.lastname: Gilon
authors.forename: A
authors.initials: A
authors.lastname: Levitzki
mesh_terms: D016475:3T3 Cells; D019883:Alkyl and Aryl Transferases; D000818:Animals; D001921:Brain / Q000201:enzymology; D002417:Cattle; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D051231:Farnesyltranstransferase; D008148:Lovastatin / Q000494:pharmacology; D051379:Mice; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014166:Transferases / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D010455:Peptides; D008148:Lovastatin; D014166:Transferases; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D051231:Farnesyltranstransferase