Progress toward rationally designed small-molecule peptide and peptidomimetic CXCR4 antagonists

Future Med Chem. 2015;7(10):1261-83. doi: 10.4155/fmc.15.64.

Abstract

Over the last 5 years, X-ray structures of CXCR4 in complex with three different ligands (the small-molecule antagonist IT1t, the polypeptide antagonist CVX15 and the viral chemokine antagonist vMIP-II) have been released. In addition to the inherent scientific value of these specific X-ray structures, they provide a reliable structural foundation for studies of the molecular interactions between CXCR4 and its key peptide ligands (CXCL12 and HIV-1 gp120), and serve as valuable templates for further development of small-molecule CXCR4 antagonists with therapeutic potential. We here review recent computational studies of the molecular interactions between CXCR4 and its peptide ligands - based on the X-ray structures of CXCR4 - and the current status of small-molecule peptide and peptidomimetic CXCR4 antagonists.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Design
  • Humans
  • Models, Molecular
  • Peptides / chemistry*
  • Peptides / pharmacology*
  • Peptidomimetics / chemistry*
  • Peptidomimetics / pharmacology*
  • Receptors, CXCR4 / antagonists & inhibitors*
  • Receptors, CXCR4 / chemistry
  • Receptors, CXCR4 / metabolism
  • Small Molecule Libraries / chemistry*
  • Small Molecule Libraries / pharmacology*

Substances

  • Peptides
  • Peptidomimetics
  • Receptors, CXCR4
  • Small Molecule Libraries