STRUCTURAL STUDIES OF POTENT CONSTRAINED RGD PEPTIDES

The three dimensional structure of a highly potent cyclic peptide antagonist of fibrinogen-glycoprotein IIbIIIa association was determined using NMR methods combined with molecular dynamics refinement. The molecule, which contains the Arg-Gly-Asp (RGD) recognition sequence, appears to be conformationally rigid in water at neutral pH, displaying a well-defined geometry of the RGD sequence. By comparison, related isomers with reduced potencies are found to have less well-defined geometries under similar conditions. The structure of this molecule may therefore provide a three-dimensional template for the design of nonpeptidic RGD mimetics.