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ID: ALA4725485

Journal: ACS Med Chem Lett

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

Authors: Ma H,Wang H,Li M,Barreto-de-Souza V,Reinecke BA,Gunta R,Zheng Y,Kang G,Nassehi N,Zhang H,An J,Selley DE,Hauser KF,Zhang Y

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.

CiteXplore: 33214847

DOI: 10.1021/acsmedchemlett.0c00444