title: In silico studies, synthesis and binding evaluation of substituted 2-pyrrolidinones as peptidomimetics of RGD tripeptide sequence.
abstract: In silico optimisation, synthesis and binding evaluation of αvβ3 integrin's affinity for precursors of a new RGD peptidomimetics family are presented. The 2-pyrrolidinone building block was obtained by condensation of l-lysine with dimethoxydihydrofuran followed by reduction. The ring was functionalized with a carboxylic acid and a guanidinium appendage. On the pyrrolidinone heterocycle, the effects on affinity of position, length and relative geometry of the two acid or basic functionalized side chains introduced on the pyrrolidinone ring have been previously evaluated by docking studies. Peptidomimetics have finally been evaluated by competition binding assays for αvβ3 integrin's affinity using radio-ligands.
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Faculté de Pharmacie, CNRS (UMR 8638), 4 Avenue de l'observatoire, 75240 Paris Cedex 06, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Toum
authors.affiliation: Université Paris 13, Sorbonne Paris Cité, Laboratoire CSPBAT, CNRS (UMR 7244), 74 Avenue M. Cachin, 93017 Bobigny, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Bolley
authors.affiliation: Université Paris 13, Sorbonne Paris Cité, Laboratoire CSPBAT, CNRS (UMR 7244), 74 Avenue M. Cachin, 93017 Bobigny, France.
authors.forename: Yoann
authors.initials: Y
authors.lastname: Lalatonne
authors.affiliation: Université Paris 13, Sorbonne Paris Cité, Laboratoire CSPBAT, CNRS (UMR 7244), 74 Avenue M. Cachin, 93017 Bobigny, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Barbey
authors.affiliation: Université Paris 13, Sorbonne Paris Cité, Laboratoire CSPBAT, CNRS (UMR 7244), 74 Avenue M. Cachin, 93017 Bobigny, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Motte
authors.affiliation: Université Paris 13, Sorbonne Paris Cité, Laboratoire CSPBAT, CNRS (UMR 7244), 74 Avenue M. Cachin, 93017 Bobigny, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Lecouvey
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Faculté de Pharmacie, CNRS (UMR 8638), 4 Avenue de l'observatoire, 75240 Paris Cedex 06, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Royer
authors.affiliation: Université Paris 13, Sorbonne Paris Cité, Laboratoire CSPBAT, CNRS (UMR 7244), 74 Avenue M. Cachin, 93017 Bobigny, France. Electronic address: nathalie.dupont@univ-paris13.fr.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dupont
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Faculté de Pharmacie, CNRS (UMR 8638), 4 Avenue de l'observatoire, 75240 Paris Cedex 06, France. Electronic address: joelle.perard@parisdescartes.fr.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Pérard-Viret
mesh_terms: D001667:Binding, Competitive; D060326:Chemistry Techniques, Synthetic; D003198:Computer Simulation; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000737:chemistry / Q000378:metabolism; D062105:Molecular Docking Simulation; D009842:Oligopeptides / Q000737:chemistry*; D057786:Peptidomimetics / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D011760:Pyrrolidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*
chemical_list: D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D057786:Peptidomimetics; D011760:Pyrrolidinones; C047981:arginyl-glycyl-aspartic acid; C028537:2-pyrrolidone
keywords: Binding; Docking; Integrin; Peptidomimetics; RGD; Synthesis