Premium
Oxorhenium‐Mediated Assembly of Noncyclic Selective Integrin Antagonists: A Combinatorial Approach
Author(s) -
Aufort Marie,
Gonera Marta,
Le Gal Julien,
Czarny Bertrand,
Le Clainche Loïc,
Thai Robert,
Dugave Christophe
Publication year - 2011
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201000700
Subject(s) - integrin , chemistry , combinatorial chemistry , chelation , structural motif , stereochemistry , receptor , biochemistry , organic chemistry
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.