title: Synthesis and evaluation of some hydroxyproline-derived peptidomimetics as isoprenyltransferase inhibitors.
abstract: CA1A2X peptidomimetics containing a modified proline at position A2 were prepared and evaluated for their ability to inhibit farnesyltransferase (FTase) and geranylgeranyltransferase I (GGTase I) in enzymatic and cell-based assays. These compounds inhibited farnesylation of H-ras in vitro in the high nanomolar to low micromolar IC50 range.
authors.affiliation: Eisai Research Institute, Andover, MA 01810, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: O'Connell
authors.forename: C A
authors.initials: CA
authors.lastname: Rowell
authors.forename: K
authors.initials: K
authors.lastname: Ackermann
authors.forename: A M
authors.initials: AM
authors.lastname: Garcia
authors.forename: M D
authors.initials: MD
authors.lastname: Lewis
authors.forename: J J
authors.initials: JJ
authors.lastname: Kowalczyk
mesh_terms: D016475:3T3 Cells; D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D051231:Farnesyltranstransferase; D011905:Genes, ras / Q000187:drug effects; D006909:Hydroxyproline / Q000737:chemistry*; D051379:Mice; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D011392:Proline; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D051231:Farnesyltranstransferase; D006909:Hydroxyproline