Jump to main content
Jump to site search


Design and synthesis of a bivalent probe targeting the putative mu opioid receptor and chemokine receptor CXCR4 heterodimer

Author affiliations

Abstract

Opioid abuse and HIV/AIDS have been defined as synergistic epidemics. Opioids can accelerate HIV replication in the immune system by up-regulating the expression of HIV co-receptor CXCR4. Several hypotheses have been suggested as the mechanism of CXCR4 modulation by opioids through their activation on the mu opioid receptor (MOR). One hypothesis is the putative heterodimerization of the MOR and CXCR4 as a mechanism of cross-talk and subsequent exacerbation of HIV replication. Bivalent chemical probes can be powerful molecular tools to characterize protein–protein interactions, and modulate the function related to such interactions. Herein we report the design and synthesis of a novel bivalent probe to explore the putative MOR–CXCR4 dimerization and its potential pharmacological role in enhancing HIV progression. The developed bivalent probe was designed with two distinct pharmacophores linked through a spacer. One pharmacophore (naltrexone) will interact with the MOR and the other (IT1t) with the CXCR4. The overall synthetic routes to prepare the bivalent probe and its corresponding monovalent controls were comprised of 18–22 steps with acceptable yields. Preliminary biological evaluation showed that the bivalent probe preserved binding affinity and functional activity at both respective receptors, supporting the initial molecular design.

Graphical abstract: Design and synthesis of a bivalent probe targeting the putative mu opioid receptor and chemokine receptor CXCR4 heterodimer

Back to tab navigation

Supplementary files

Article information


Submitted
10 Sep 2019
Accepted
18 Oct 2019
First published
19 Dec 2019

This article is Open Access

RSC Med. Chem., 2020, Advance Article
Article type
Research Article

Design and synthesis of a bivalent probe targeting the putative mu opioid receptor and chemokine receptor CXCR4 heterodimer

B. A. Reinecke, G. Kang, Y. Zheng, S. Obeng, H. Zhang, D. E. Selley, J. An and Y. Zhang, RSC Med. Chem., 2020, Advance Article , DOI: 10.1039/C9MD00433E

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material and it is not used for commercial purposes.

Reproduced material should be attributed as follows:

  • For reproduction of material from NJC:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
  • For reproduction of material from PCCP:
    [Original citation] - Published by the PCCP Owner Societies.
  • For reproduction of material from PPS:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
  • For reproduction of material from all other RSC journals:
    [Original citation] - Published by The Royal Society of Chemistry.

Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.


Social activity

Search articles by author

Spotlight

Advertisements