Synthesis and evaluation of pseudopeptide analogues of a specific CXCR4 inhibitor, T140: the insertion of an (E)-alkene dipeptide isostere into the betaII'-turn moiety

Bioorg Med Chem Lett. 2002 Mar 25;12(6):923-8. doi: 10.1016/s0960-894x(02)00041-0.

Abstract

A 14-residue peptide, T140, strongly inhibits the T-cell line-tropic HIV-1 (X4-HIV-1) infection, since this peptide functions as a specific antagonist against a chemokine receptor, CXCR4. T140 takes an antiparallel beta-sheet structure with a type II' beta-turn. In the present paper, we have designed and synthesized several T140 analogues, in which an (E)-alkene dipeptide isostere was inserted into the type II' beta-turn moiety, as a bridging study to develop nonpeptidic CXCR4 inhibitors. It has been proven that the turn region of T140 can be replaced by the above surrogate with the maintenance of strong anti-HIV activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / pharmacology
  • Calcium Signaling / drug effects
  • Cell Division / drug effects
  • Dipeptides / chemistry
  • HIV-1 / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / pharmacology
  • Protein Structure, Secondary
  • Receptors, CXCR4 / antagonists & inhibitors*
  • Tumor Cells, Cultured

Substances

  • Anti-HIV Agents
  • Dipeptides
  • Oligopeptides
  • Receptors, CXCR4
  • T140 peptide