Breaking the dogma of the metal-coordinating carboxylate group in integrin ligands: introducing hydroxamic acids to the MIDAS to tune potency and selectivity.
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.
Heckmann
Dominik
D
Institute for Advanced Study, TU München, Department Chemie, Lichtenbergstrasse 4, 85747 Garching, Germany.
Laufer
Burkhardt
B
Marinelli
Luciana
L
Limongelli
Vittorio
V
Novellino
Ettore
E
Zahn
Grit
G
Stragies
Roland
R
Kessler
Horst
H