Breaking the Dogma of the Metal‐Coordinating Carboxylate Group in Integrin Ligands: Introducing Hydroxamic Acids to the MIDAS To Tune Potency and Selectivity

Abstract

A suitable substitute: All integrin receptors bind their ligands, which contain an aspartate residue, in the metal-ion- dependent adhesion site (MIDAS). So far all attempts to replace the carboxyl group of aspartate with other, pharmacologically favorable isosteric groups have failed. Now it has been shown that a hydroxamic acid group can replace the carboxyl group; the resulting ligand retains its high binding activity. The picture shows one such ligand in the binding site of alphavbeta3.