title: Synthesis and biological activity of ras farnesyl protein transferase inhibitors. Tetrapeptide analogs with amino methyl and carbon linkages.
abstract: Replacement of the central amino methylene linkage of C[psi CH2NH]A[psi CH2NH]AX tetrapeptide inhibitors with carbon tethers led to compounds with potency in the nanomolar range. Some of the more potent olefinic compounds inhibit Ras processing in intact v-ras transformed NIH 3T3 cells with IC50 values in the 0.1 to 1 microM range, and inhibit selectively the anchorage-independent growth of H-ras transformed Rat1 cells at 10 microM.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486.
authors.forename: J S
authors.initials: JS
authors.lastname: Wai
authors.forename: D L
authors.initials: DL
authors.lastname: Bamberger
authors.forename: T E
authors.initials: TE
authors.lastname: Fisher
authors.forename: S L
authors.initials: SL
authors.lastname: Graham
authors.forename: R L
authors.initials: RL
authors.lastname: Smith
authors.forename: J B
authors.initials: JB
authors.lastname: Gibbs
authors.forename: S D
authors.initials: SD
authors.lastname: Mosser
authors.forename: A I
authors.initials: AI
authors.lastname: Oliff
authors.forename: D L
authors.initials: DL
authors.lastname: Pompliano
authors.forename: E
authors.initials: E
authors.lastname: Rands
mesh_terms: D016475:3T3 Cells; D019883:Alkyl and Aryl Transferases; D000595:Amino Acid Sequence; D000818:Animals; D002472:Cell Transformation, Viral; D011905:Genes, ras; D051379:Mice; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014166:Transferases / Q000037:antagonists & inhibitors*
chemical_list: D009842:Oligopeptides; D014166:Transferases; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase