Bivalent Ligand Aiming Putative Mu Opioid Receptor and Chemokine Receptor CXCR4 Dimers in Opioid Enhanced HIV-1 Entry.

ACS Medicinal Chemistry Letters
Hongguang MaYan Zhang

Abstract

A bivalent compound 1a featuring both a mu opioid receptor (MOR) and a CXCR4 antagonist pharmacophore (naltrexone and IT1t) was designed and synthesized. Further binding and functional studies demonstrated 1a acting as a MOR and a CXCR4 dual antagonist with reasonable binding affinities at both receptors. Furthermore, compound 1a seemed more effective than a combination of IT1t and naltrexone in inhibiting HIV entry at the presence of morphine. Additional molecular modeling results suggested that 1a may bind with the putative MOR-CXCR4 heterodimer to induce its anti-HIV activity. Collectively, bivalent ligand 1a may serve as a promising lead to develop chemical probes targeting the putative MOR-CXCR4 heterodimer in comprehending opioid exacerbated HIV-1 invasion.

References

Jan 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·P L EarlB Moss
Jul 20, 2002·Proceedings of the National Academy of Sciences of the United States of America·Imre SzaboThomas J Rogers
May 3, 2003·Virology·Amber D SteeleThomas J Rogers
Nov 14, 2003·Journal of Medicinal Chemistry·John L NeumeyerJean M Bidlack
Sep 29, 2004·Journal of Substance Abuse Treatment·David A FiellinThomas R Kosten
Apr 16, 2005·Cell Death and Differentiation·M KaulS A Lipton
Nov 2, 2005·Neurotoxicity Research·K F HauserP E Knapp
Aug 10, 2007·Expert Opinion on Investigational Drugs·Sandra D ComerGary K Hulse
Feb 7, 2008·Journal of Leukocyte Biology·Christine HappelThomas J Rogers
Dec 17, 2008·Current Drug Discovery Technologies·Isabelle Berque-BestelRalf Jockers
Dec 31, 2008·Journal of Medicinal Chemistry·Yaguo ZhengPhilip S Portoghese
Nov 7, 2009·Bioorganic & Medicinal Chemistry Letters·Shijun ZhangPhilip S Portoghese
Apr 7, 2010·Journal of Medicinal Chemistry·Yvonne RookThomas Winckler
Mar 23, 2012·Nature·Aashish ManglikSébastien Granier
May 18, 2012·Current HIV Research·Kurt F HauserPamela E Knapp
Aug 22, 2012·Cold Spring Harbor Perspectives in Medicine·Craig B WilenRobert W Doms
Oct 3, 2012·Cold Spring Harbor Perspectives in Medicine·Wei-Shau Hu, Stephen H Hughes
Jun 27, 2013·Proceedings of the National Academy of Sciences of the United States of America·Eyup AkgünPhilip S Portoghese
Dec 3, 2013·Journal of Immunological Methods·Marcella Sarzotti-KelsoeDavid C Montefiori
Aug 28, 2014·Current Topics in Medicinal Chemistry·Christopher Kent Arnatt, Yan Zhang
Dec 30, 2014·Expert Opinion on Drug Metabolism & Toxicology·Santosh KumarAnil Kumar
Jan 16, 2015·Nature Reviews. Neuroscience·Stéphane Mélik ParsadaniantzAnnabelle Réaux-Le Goazigo
Feb 19, 2016·Scientific Reports·Teresa KasererDaniela Schuster
Jul 28, 2016·Nature Communications·Harald HübnerPeter Gmeiner
Oct 26, 2016·Bioorganic & Medicinal Chemistry·Christopher K ArnattYan Zhang

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.