title: Morpholine-based RGD-cyclopentapeptides as alphavbeta3/alphavbeta5 integrin ligands: role of configuration towards receptor binding affinity.
abstract: Two c[RGDfX] cyclopeptides, having either L- or D-morpholine-3-COOH (Mor) as the X amino acid were developed as ligands for alpha(v)beta(3)/alpha(v)beta(5) integrins. Biological assays showed only d-Mor-containing cyclopentapeptide capable to bind alpha(v)beta(3) integrin with a low nanomolar affinity according to a two-site model, thus revealing a connection between the configuration of Mor and the preferred binding to alpha(v)beta(3) integrin. Conformational analysis showed different structural preferences for the two peptides induced by the two enantiomeric cyclic amino acids, suggesting a role of the stereochemistry of Mor on the overall peptide conformation and on the presentation of the pharmacophoric Arg and Asp side chains.
authors.affiliation: Dipartimento di Chimica Organica Ugo Schiff, Università degli Studi di Firenze, Polo Scientifico e Tecnologico, Sesto Fiorentino, FI, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Cini
authors.forename: Andrea
authors.initials: A
authors.lastname: Trabocchi
authors.forename: Gloria
authors.initials: G
authors.lastname: Menchi
authors.forename: Anna
authors.initials: A
authors.lastname: Bottoncetti
authors.forename: Silvia
authors.initials: S
authors.lastname: Raspanti
authors.forename: Alberto
authors.initials: A
authors.lastname: Pupi
authors.forename: Antonio
authors.initials: A
authors.lastname: Guarna
mesh_terms: D001665:Binding Sites; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009025:Morpholines / Q000737:chemistry / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D019030:Receptors, Vitronectin / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D039302:Integrin alphaVbeta3; D008024:Ligands; D009025:Morpholines; D009842:Oligopeptides; D010456:Peptides, Cyclic; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; C047981:arginyl-glycyl-aspartic acid; C037574:morpholine