Different stereochemical requirements for CXCR4 binding and signaling functions as revealed by an anti-HIV, D-amino acid-containing SMM-chemokine ligand

J Med Chem. 2005 Dec 15;48(25):7923-4. doi: 10.1021/jm050829u.

Abstract

Human immunodeficiency virus type 1 (HIV-1) uses a chemokine receptor, usually CXCR4 or CCR5, for entry into the target cells. Here, we used a chemical biology approach to demonstrate that binding and signaling domains in CXCR4 are possibly distinct and separate, as the new analogue, D(1-10)-vMIP-II-(9-68)-SDF-1alpha (RCP222), could not activate CXCR4 despite the fact that its binding activity was comparable to that of stromal cell-derived factor (SDF)-1alpha, the only natural ligand of CXCR4.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Amino Acids / chemistry*
  • Anti-HIV Agents / chemistry*
  • Anti-HIV Agents / pharmacology
  • Binding, Competitive
  • Calcium / metabolism
  • Cell Line
  • Chemokine CXCL12
  • Chemokines / chemistry
  • Chemokines / metabolism*
  • Chemokines / pharmacology
  • Chemokines, CXC / metabolism
  • HIV-1 / drug effects
  • Humans
  • Ligands
  • Molecular Conformation
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Radioligand Assay
  • Receptors, CXCR4 / agonists
  • Receptors, CXCR4 / metabolism
  • Receptors, CXCR4 / physiology*
  • Signal Transduction

Substances

  • Amino Acids
  • Anti-HIV Agents
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines
  • Chemokines, CXC
  • D(1-10)-vMIP-II-(9-68)-SDF-1alpha
  • Ligands
  • Receptors, CXCR4
  • vMIP-II
  • Calcium