title: Oxorhenium-mediated assembly of noncyclic selective integrin antagonists: a combinatorial approach.
abstract: The parallel oxorhenium-mediated assembly of 288 noncyclic RGD analogues is reported. All complexes contain a NS(2) +S chelating motif that enables the unambiguous coordination of the oxorhenium and oxotechnetium cores. In this study, "modules S" contain a variety of pending guanidinium groups whereas the "NS(2)  modules" are made of a series of N-acylated amino acids. Combination of sets of "NS(2) " and "S modules" together with tetrabutylammonium tetrachlorooxorhenate gave the corresponding oxorhenium complexes in good yields and satisfactory purities. Evaluation of these metalloconstructs towards integrins α(V) β(3) , α(IIb) β(3) , and α(V) β(5)  led to the identification of micromolar and submicromolar antagonists of theses integrins. These compounds exhibit interesting selectivities and promise attractive applications for the molecular imaging of integrin-dependent pathologies.
authors.affiliation: CEA, iBiTecS, Service d'Ingénierie Moléculaire des Protéines, Bâtiment 152, CEA/Saclay, Gif-sur-Yvette 91191, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Aufort
authors.forename: Marta
authors.initials: M
authors.lastname: Gonera
authors.forename: Julien
authors.initials: J
authors.lastname: Le Gal
authors.forename: Bertrand
authors.initials: B
authors.lastname: Czarny
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Clainche
authors.forename: Robert
authors.initials: R
authors.lastname: Thai
authors.forename: Christophe
authors.initials: C
authors.lastname: Dugave
mesh_terms: D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D020128:Inhibitory Concentration 50; D016023:Integrins / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D057786:Peptidomimetics; D012211:Rhenium / Q000737:chemistry*
chemical_list: D016023:Integrins; D009942:Organometallic Compounds; D010455:Peptides; D057786:Peptidomimetics; C015428:perrhenate; D012211:Rhenium