title: 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.
authors.affiliation: Institute for Advanced Study, TU München, Department Chemie, Lichtenbergstrasse 4, 85747 Garching, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Heckmann
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Laufer
authors.forename: Luciana
authors.initials: L
authors.lastname: Marinelli
authors.forename: Vittorio
authors.initials: V
authors.lastname: Limongelli
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Grit
authors.initials: G
authors.lastname: Zahn
authors.forename: Roland
authors.initials: R
authors.lastname: Stragies
authors.forename: Horst
authors.initials: H
authors.lastname: Kessler