title: Non-thiol farnesyltransferase inhibitors: utilization of an aryl binding site by 5-arylacryloylaminobenzophenones.
abstract: We recently described a novel aryl binding site of farnesyltransferase. The 2-naphthylacryloyl residue was developed as an appropriate substituent for our benzophenone-based AAX-peptidomimetic capable of occupying this binding site, resulting in a non-thiol farnesyltransferase inhibitor with nanomolar activity. The activity of this inhibitor is readily explained on the basis of docking studies which show the 2-naphthyl residue fitting into the aryl binding site.
authors.affiliation: Institut für Pharmazeutische Chemie, Philipps-Universität Marburg, Marbacher Weg 6, D-35032 Marburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Mitsch
authors.forename: Markus
authors.initials: M
authors.lastname: Böhm
authors.forename: Pia
authors.initials: P
authors.lastname: Wissner
authors.forename: Isabel
authors.initials: I
authors.lastname: Sattler
authors.forename: Martin
authors.initials: M
authors.lastname: Schlitzer
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D001577:Benzophenones / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D051231:Farnesyltranstransferase; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008958:Models, Molecular; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology; D011485:Protein Binding; D013329:Structure-Activity Relationship; D015003:Yeasts / Q000201:enzymology
chemical_list: D001577:Benzophenones; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase