Nonpeptide RGD antagonists: a novel class of mimetics, the 5,8-disubstituted 1-azabicyclo[5.2.0]nonan-2-one lactam

Bioorg Med Chem Lett. 2003 May 5;13(9):1561-4. doi: 10.1016/s0960-894x(03)00181-1.

Abstract

The 1-azabicyclo[5.2.0]nonan-2-one lactam 1 adequately substituted on both cycles A and B as scaffolds mimics the conformationally constrained beta-turn of the tripeptide RGD signaling motif of fibronectin. Using an in vitro assay, we establish that trans diastereoisomer 1b dissociates a soluble fibronectin-integrin alpha(5)beta(1) complex at concentrations comparable to those of a linear RGDS peptide as a competitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Bridged Bicyclo Compounds / chemical synthesis*
  • Bridged Bicyclo Compounds / pharmacology
  • Drug Design
  • Fibronectins / chemistry
  • Integrin alpha5beta1 / chemistry
  • Lactams / chemical synthesis*
  • Lactams / chemistry
  • Lactams / pharmacology
  • Molecular Mimicry
  • Oligopeptides / antagonists & inhibitors*
  • Oligopeptides / chemistry
  • Stereoisomerism

Substances

  • 1-azabicyclo(5.2.0)nonan-2-one lactam
  • Bridged Bicyclo Compounds
  • Fibronectins
  • Integrin alpha5beta1
  • Lactams
  • Oligopeptides
  • arginyl-glycyl-aspartic acid