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Cover Picture: Oxorhenium‐Mediated Assembly of Noncyclic Selective Integrin Antagonists: A Combinatorial Approach (ChemBioChem 4/2011)
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 - Reports
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201190010
Subject(s) - integrin , chemistry , affinities , binding affinities , combinatorial chemistry , stereochemistry , computational biology , receptor , biochemistry , biology
The cover picture shows the TcO 3+ ‐ or ReO 3+ ‐mediated assembly of independent chemical modules to form a library of antagonists of integrins, αβ‐heterodimeric integral proteins implicated in cancer development (bottom). Parallel combination of 36 “NS 2 modules” bearing a carboxylate (module 15d ) and eight “S modules” grafted with a guanidinium group (module D ) together with ReO 3+ enabled the synthesis of 288 oxorhenium RGD mimetics. Library screening led to the selection of six complexes that exhibit micromolar and sub‐micromolar affinities for integrins α V β 3 , α IIb β 3 and α V β 5 and interesting selectivities. Complex Re– D15d , shown here, was identified as the antagonist with the greatest affinity and selectivity (IC 50 =240 nm for α V β 3 ). The corresponding Tc– D15d complex exhibited a satisfactory stability in mice plasma. Oxotechnetium‐assembled RGD mimetics should be assayed for the molecular imaging of integrin‐dependent cancer progression in nude mice bearing a human tumor xenograft. For more information see the paper by C. Dugave et al. on p. 583 ff.