Novel and selective alpha(v)beta3 receptor peptide antagonist: design, synthesis, and biological behavior

J Med Chem. 2006 Jun 1;49(11):3416-20. doi: 10.1021/jm060233m.

Abstract

Among RGD-dependent integrins, the alpha(v)beta3 receptor has recently received increasing attention as a therapeutic target because of its critical role in tumor-induced angiogenesis and metastasis formation. Here, we describe a new peptide antagonist of alpha(v)beta3 receptor, designed on the basis of the crystal structure of integrin alpha(v)beta3 in complex with c(RGDf[NMe]V) and the NMR structure of echistatin. Cell adhesion assays have demonstrated that the peptide is a potent and selective antagonist of the alpha(v)beta3 receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion / drug effects
  • Crystallography, X-Ray
  • Drug Design
  • Humans
  • Integrin alphaVbeta3 / antagonists & inhibitors*
  • Integrin alphaVbeta3 / biosynthesis
  • Integrin alphaVbeta3 / chemistry
  • Integrins / biosynthesis
  • Intercellular Signaling Peptides and Proteins
  • K562 Cells
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Mimicry
  • Molecular Structure
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry*
  • Oligopeptides / pharmacology
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Peptides / pharmacology
  • Radioligand Assay
  • Receptors, Vitronectin / biosynthesis
  • Vitronectin / physiology

Substances

  • Integrin alphaVbeta3
  • Integrins
  • Intercellular Signaling Peptides and Proteins
  • Oligopeptides
  • Peptides
  • Receptors, Vitronectin
  • Vitronectin
  • integrin alphaVbeta5
  • echistatin
  • arginyl-glycyl-aspartic acid