title: Multiple N-methylation by a designed approach enhances receptor selectivity.
abstract: An unselective cyclic peptide integrin ligand was sequentially N-methylated by a designed approach, where only the externally oriented (solvent exposed) amide bonds were N-methylated. The N-methylation resulted in tremendous enhancement in selectivity among the different integrin receptor subtypes (alpha5beta1, alphavbeta3, and alphaIIbbeta3). Conformational and docking studies were performed, which suggested that the receptor selectivity is principally caused by reduced backbone flexibility due to N-methylation.
authors.affiliation: Center for Integrated Protein Science at the Department Chemie, Lehrstuhl II für Organische Chemie, Technische Universität München, Lichtenbergstrasse 4, Garching D85747, Germany.
authors.forename: Jayanta
authors.initials: J
authors.lastname: Chatterjee
authors.forename: Oded
authors.initials: O
authors.lastname: Ovadia
authors.forename: Grit
authors.initials: G
authors.lastname: Zahn
authors.forename: Luciana
authors.initials: L
authors.lastname: Marinelli
authors.forename: Amnon
authors.initials: A
authors.lastname: Hoffman
authors.forename: Chaim
authors.initials: C
authors.lastname: Gilon
authors.forename: Horst
authors.initials: H
authors.lastname: Kessler
mesh_terms: D001665:Binding Sites; D015195:Drug Design; D039081:Integrin alpha5beta1 / Q000737:chemistry*; D039302:Integrin alphaVbeta3 / Q000737:chemistry*; D008024:Ligands; D008745:Methylation; D008958:Models, Molecular; D008968:Molecular Conformation; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D039081:Integrin alpha5beta1; D039302:Integrin alphaVbeta3; D008024:Ligands; D009842:Oligopeptides; D010456:Peptides, Cyclic; D019039:Platelet Glycoprotein GPIIb-IIIa Complex