Anti-HIV activity and conformational studies of peptides derived from the C-terminal sequence of SDF-1

J Med Chem. 2004 Jun 3;47(12):3058-64. doi: 10.1021/jm031067a.

Abstract

The entry of the human immunodeficiency virus type 1 (HIV-1) into target cells requires the interaction of viral envelope glycoprotein, gp120, with the human CD4 glycoprotein and a chemokine receptor, usually CCR5 or CXCR4. The natural ligand for CXCR4 is the chemokine SDF-1 that inhibits entry and replication of X4 HIV-1 strains. SDF-1 is produced in two forms, SDF-1alpha (68 residues) and SDF-1beta (72 residues); the difference between them lies in the additional four C-terminal amino acids in the SDF-1beta sequence. Despite the relevance of the N-terminal site in determining the SDF anti HIV-1 activity, SDF-1beta has a stronger activity than SDF-1alpha. Here we demonstrate that a synthetic peptide mapped on the C-terminus of SDF-1beta presents inhibitory activity, whereas an analogue reproducing the C-terminal trait of SDF-1alpha does not show any activity. The opposite biological effect of the two peptides correlates with the type of interaction they each have with heparin and chondroitin sulfate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology
  • Cell Line, Tumor
  • Chemokine CXCL12
  • Chemokines, CXC / chemistry*
  • Chondroitin Sulfates / chemistry
  • Circular Dichroism
  • Cytokines / chemistry*
  • HIV / drug effects
  • Heparin / chemistry
  • Humans
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptides / chemical synthesis*
  • Peptides / chemistry
  • Peptides / pharmacology
  • Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • Cytokines
  • Peptide Fragments
  • Peptides
  • Heparin
  • Chondroitin Sulfates