Structure-activity relationship study of CXCR4 antagonists bearing the cyclic pentapeptide scaffold: identification of the new pharmacophore

Org Biomol Chem. 2008 Dec 7;6(23):4374-7. doi: 10.1039/b812029c. Epub 2008 Oct 17.

Abstract

A highly potent CXCR4 antagonist 2 [cyclo (-D-Tyr1-Arg2-Arg3-Nal4-Gly5-)] has previously been identified by screening cyclic pentapeptide libraries that were designed based on pharmacophore residues of a 14-residue peptidic CXCR4 antagonist 1. In the present study, D-Tyr and Arg in peptide 2 were replaced by a bicyclic aromatic amino acid and a cationic amino acid, respectively, and their binding activity for CXCR4 was evaluated for identification of the novel pharmacophore.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Cell Line
  • Drug Discovery*
  • HIV-1 / drug effects
  • Humans
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry*
  • Oligopeptides / pharmacology*
  • Oligopeptides / toxicity
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / chemistry*
  • Peptides, Cyclic / pharmacology*
  • Peptides, Cyclic / toxicity
  • Receptors, CXCR4 / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Tyrosine / chemistry

Substances

  • Oligopeptides
  • Peptides, Cyclic
  • Receptors, CXCR4
  • Tyrosine