title: Design, synthesis, and pharmacological evaluation of new farnesyl protein transferase inhibitors.
abstract: New CA(1)A(2)X peptidomimetics are described as Ras farnesyl transferase inhibitors (FTIs). They include cysteine and methionine as mimetics of the C-terminus sequence of farnesylated proteins. Furthermore, cysteine was replaced by heterocycles, taking into account the role of zinc and the metabolic instability of amino acids. The molecular docking of 8 in the active site of the enzyme and the pharmacological evaluation of the compounds are illustrative of a new class of FTIs.
authors.affiliation: Institut de Chimie Pharmaceutique Albert Lespagnol, EA 2692, Université de Lille 2, 3 rue du Professeur Laguesse, BP 83, 59006 Lille, France.
authors.forename: Raymond
authors.initials: R
authors.lastname: Houssin
authors.forename: Jean
authors.initials: J
authors.lastname: Pommery
authors.forename: Marie-Catherine
authors.initials: MC
authors.lastname: Salaün
authors.forename: Sophie
authors.initials: S
authors.lastname: Deweer
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Goossens
authors.forename: Philippe
authors.initials: P
authors.lastname: Chavatte
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hénichart
mesh_terms: D016475:3T3 Cells; D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000818:Animals; D002463:Cell Membrane Permeability; D003545:Cysteine / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008715:Methionine / Q000737:chemistry; D051379:Mice; D008958:Models, Molecular; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D010455:Peptides; D013844:Thiazoles; D008715:Methionine; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase; D003545:Cysteine