Files and links (1)
Accepted (AM)Open Access (License Unspecified), Open
Journal article
Bifunctional Chimera That Coordinately Targets Human Immunodeficiency Virus 1 Envelope gp120 and the Host-Cell CCR5 Coreceptor at the Virus-Cell Interface
Journal of medicinal chemistry, v 61(11), pp 5020-5033
14 Jun 2018
PMID: 29767965
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
To address the urgent need for new agents to reduce the global occurrence and spread of AIDS, we investigated the underlying hypothesis that antagonists of the HIV-1 envelope (Env) gp120 protein and the host-cell coreceptor (CoR) protein can be covalently joined into bifunctional synergistic combinations with improved antiviral capabilities. A synthetic protocol was established to covalently combine a CCR5 small-molecule antagonist and a gp120 peptide triazole antagonist to form the bifunctional chimera. Importantly, the chimeric inhibitor preserved the specific targeting properties of the two separate chimera components and, at the same time, exhibited low to subnanomolar potencies in inhibiting cell infection by different pseudoviruses, which were substantially greater than those of a noncovalent mixture of the individual components. The results demonstrate that targeting the virus cell interface with a single molecule can result in improved potencies and also the introduction of new phenotypes to the chimeric inhibitor, such as the irreversible inactivation of HIV-1.
Metrics
Details
- Title
- Bifunctional Chimera That Coordinately Targets Human Immunodeficiency Virus 1 Envelope gp120 and the Host-Cell CCR5 Coreceptor at the Virus-Cell Interface
- Creators
- Adel A. Rashad - Drexel Univ, Dept Biochem & Mol Biol, Coll Med, Philadelphia, PA 19102 USALi-Rui Song - Soochow UniversityAndrew P. Holmes - Drexel Univ, Dept Biochem & Mol Biol, Coll Med, Philadelphia, PA 19102 USAKriti Acharya - Drexel Univ, Dept Biochem & Mol Biol, Coll Med, Philadelphia, PA 19102 USAShiyu Zhang - Drexel UniversityZhi-Long Wang - Shanghai Institute of Materia MedicaEbony Gary - Drexel Univ, Dept Med, Coll Med, Philadelphia, PA 19102 USAXin Xie - Shanghai Institute of Materia MedicaVanessa Pirrone - Drexel UniversityMichele A. Kutzler - Drexel UniversityYa-Qiu Long - Shanghai Institute of Materia MedicaIrwin Chaiken - Drexel University
- Publication Details
- Journal of medicinal chemistry, v 61(11), pp 5020-5033
- Publisher
- American Chemical Society; Washington, DC
- Number of pages
- 14
- Grant note
- R01AI106633; P01GMS6550 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01AI106633 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) 81761128022; 81361120410; 81325020 / National Natural Science Foundation of China; National Natural Science Foundation of China (NSFC) P01GM056550 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Microbiology and Immunology; Infectious Diseases (and HIV Medicine)
- Web of Science ID
- WOS:000435613100024
- Scopus ID
- 2-s2.0-85047402021
- Other Identifier
- 991019167472304721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Chemistry, Medicinal