Paradoxical downregulation of CXC chemokine receptor 4 induced by polyphemusin II-derived antagonists

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Updated: May 23, 2026

A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 4
06:56

A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 4

Published on: March 10, 2018

Ryo Masuda1, Shinya Oishi, Noriko Tanahara

  • 1Graduate School of Pharmaceutical Sciences, Kyoto University , Sakyo-ku, Kyoto 606-8501, Japan.

Bioconjugate Chemistry
|April 11, 2012
PubMed

Insights

The CXCR4 antagonist T140 and its derivatives promote receptor internalization, which contributes to their anti-HIV activity. This mechanism involves the translocation of CXC chemokine receptor 4 (CXCR4) into the perinuclear region.

Area of Science:

  • Molecular Biology
  • Immunology
  • Virology

Background:

  • CXC chemokine receptor 4 (CXCR4) is a key G protein-coupled receptor involved in HIV-1 entry.
  • The stromal cell derived factor-1 (SDF-1)/CXCR4 axis regulates immune cell trafficking and cancer metastasis.
  • The CXCR4 antagonist T140 was previously developed from polyphemusin II.

Purpose of the Study:

  • To investigate the localization of CXCR4 upon stimulation with its ligand SDF-1 and the antagonist T140.
  • To elucidate the mechanism underlying the anti-HIV activity of T140 derivatives.

Main Methods:

  • Utilized fluorescently labeled SDF-1 and T140 derivatives.
  • Employed a specific labeling technique for cellular-membrane CXCR4.
  • Monitored receptor localization and internalization using microscopy and a tag-probe system.

Main Results:

  • Fluorescent T140 derivatives induced translocation of CXCR4 to the perinuclear region, similar to SDF-1.
  • T140 derivative-mediated internalization of CXCR4 was confirmed using a coiled-coil tag-probe system.
  • Antagonistic and anti-HIV activities of T140 derivatives are linked to receptor internalization.

Conclusions:

  • Antagonist-mediated internalization of CXCR4 is a significant mechanism contributing to the anti-HIV efficacy of T140 derivatives.
  • Understanding CXCR4 dynamics provides insights into HIV-1 entry inhibition.
  • This study highlights the therapeutic potential of targeting CXCR4 internalization.

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