Molecular dynamics reveal that isoDGR-containing cyclopeptides are true αvβ3 antagonists unable to promote integrin allostery and activation

Angew Chem Int Ed Engl. 2012 Jul 27;51(31):7702-5. doi: 10.1002/anie.201202032. Epub 2012 Jun 20.

Abstract

Ain't got that swing(-out): The cyclopeptide isoDGR is emerging as a new αvβ3 integrin binding motif. Agreement between the results of computational and biochemical studies reveals that isoDGR-containing cyclopeptides are true αvβ3 integrin antagonists that block αvβ3 in its inactive conformation (see scheme). isoDGR-based ligands may give αvβ3 antagonists without paradoxical effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation
  • Integrin alphaVbeta3 / antagonists & inhibitors*
  • Integrin alphaVbeta3 / metabolism
  • Models, Molecular
  • Molecular Dynamics Simulation*
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology*
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacology*

Substances

  • Integrin alphaVbeta3
  • Oligopeptides
  • Peptides, Cyclic
  • arginyl-glycyl-aspartic acid