Investigation of Conformational Specificity at GPIIb/IIIa: Evaluation of Conformationally Constrained RGD Peptides

J Med Chem. 1992 Oct 16;35(21):3962-9. doi: 10.1021/jm00099a026.

Abstract

RGD-containing proteins and peptides are known to bind to the platelet GPIIb/IIIa receptor and inhibit platelet aggregation. That a conformational component to the specificity exists is suggested by significantly lower activity of linear RGD analogs relative to closely related cyclic peptides and small proteins containing the RGD sequence. Recently, conformations for a suite of RGD containing cyclic peptides have been defined by NMR-based methods and, for one molecule, by X-ray diffraction. We report here the NMR-based conformational analysis of an additional cyclic peptide, cyclo(Pro-Arg-Gly-Asp-D-Pro-Gly), and compare the conformational variations in the suite of peptides and related analogs. Biological activity data for these peptides shows a preference of the platelet GPIIb/IIIa receptor for one conformation of the RGD sequence, but suggests its ability to bind a second, distinct conformation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Humans
  • In Vitro Techniques
  • Magnetic Resonance Spectroscopy
  • Molecular Sequence Data
  • Oligopeptides / chemistry
  • Oligopeptides / metabolism*
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / metabolism*
  • Platelet Membrane Glycoproteins / metabolism*
  • Protein Conformation
  • Substrate Specificity

Substances

  • Oligopeptides
  • Peptides, Cyclic
  • Platelet Membrane Glycoproteins
  • arginyl-glycyl-aspartic acid