A low-molecular-weight inhibitor against the chemokine receptor CXCR4: a strong anti-HIV peptide T140

Biochem Biophys Res Commun. 1998 Dec 30;253(3):877-82. doi: 10.1006/bbrc.1998.9871.

Abstract

T22 ([Tyr5,12, Lys7]-polyphemusin II) is an 18-residue peptide amide, which has strong anti-HIV activity. T22 inhibits the T cell line-tropic (T-tropic) HIV-1 infection through its specific binding to a chemokine receptor CXCR4, which serves as a coreceptor for the entry of T-tropic HIV-1 strains. Herein, we report our finding of novel 14-residue CXCR4 inhibitors, T134 and T140, on the basis of the T22 structure. In the assays we examined, T140 showed the highest inhibitory activity against HIV-1 entry and the strongest inhibitory effect on the binding of an anti-CXCR4 monoclonal antibody (12G5) to CXCR4 among all the CXCR4 inhibitors that have been reported up to now.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / toxicity
  • Antimicrobial Cationic Peptides*
  • Cells, Cultured
  • Chemokine CXCL12
  • Chemokines, CXC / pharmacology
  • Circular Dichroism
  • DNA-Binding Proteins / chemistry
  • HIV-1 / drug effects*
  • Heterocyclic Compounds / pharmacology
  • Molecular Sequence Data
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology*
  • Oligopeptides / toxicity
  • Peptides / chemistry
  • Peptides / pharmacology
  • Peptides, Cyclic / chemistry
  • Receptors, CXCR4 / antagonists & inhibitors*
  • T-Lymphocytes / virology*

Substances

  • Anti-HIV Agents
  • Antimicrobial Cationic Peptides
  • Chemokine CXCL12
  • Chemokines, CXC
  • DNA-Binding Proteins
  • Heterocyclic Compounds
  • N-alpha-acetyl-nona-D-arginine amide acetate
  • Oligopeptides
  • Peptides
  • Peptides, Cyclic
  • Receptors, CXCR4
  • T134 peptide
  • TW 70
  • tachyplesin peptide, Tachypleus tridentatus
  • polyphemusin II
  • T22 protein, synthetic
  • T140 peptide
  • plerixafor