Files and links (1)
Published, Version of Record (VoR)Open Access (License Unspecified), Open
Journal article
Identification of gp120 Residue His105 as a Novel Target for HIV-1 Neutralization by Small-Molecule CD4-Mimics
ACS medicinal chemistry letters, v 12(11), pp 1824-1831
11 Nov 2021
PMID: 34795873
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The design and synthesis of butyl chain derivatives at the indane ring 3-position of our lead CD4-mimetic compound BNM-III-170 that inhibits human immunodeficiency virus (HIV-1) infection are reported. Optimization efforts were guided by crystallographic and computational analysis of the small-molecule ligands of the Phe43 cavity of the envelope glycoprotein gp120. Biological evaluation of 11-21 revealed that members of this series of CD4-mimetic compounds are able to inhibit HIV-1 viral entry into target cells more potently and with greater breadth compared to BNM-III-170. Crystallographic analysis of the binding pocket of 14, 16, and 17 revealed a novel hydrogen bonding interaction between His105 and a primary hydroxyl group on the butyl side chain. Further optimization of this interaction with the His105 residue holds the promise of more potent CD4-mimetic compounds.
Metrics
Details
- Title
- Identification of gp120 Residue His105 as a Novel Target for HIV-1 Neutralization by Small-Molecule CD4-Mimics
- Creators
- Christopher J. Fritschi - University of PennsylvaniaShuaiyi Liang - Columbia UniversityMohammadjavad Mohammadi - Drexel UniversitySaumya Anang - Dana-Farber Cancer InstituteFrancesca Moraca - Drexel UniversityJunhua Chen - University of PennsylvaniaNavid Madani - Dana-Farber Cancer InstituteJoseph G. Sodroski - Dana-Farber Cancer InstituteCameron F. Abrams - Drexel UniversityWayne A. Hendrickson - Columbia UniversityAmos B. Smith - University of Pennsylvania
- Publication Details
- ACS medicinal chemistry letters, v 12(11), pp 1824-1831
- Publisher
- American Chemical Society; Washington, DC
- Number of pages
- 8
- Grant note
- Vagelos Institute for Energy Science and Technology NSF CHE-1827457 / NSF Major Research Instrumentation Program; National Science Foundation (NSF); NSF - Directorate for Mathematical & Physical Sciences (MPS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Chemical and Biological Engineering
- Web of Science ID
- WOS:000719794000027
- Scopus ID
- 2-s2.0-85118879664
- Other Identifier
- 991019167975404721
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
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Chemistry, Medicinal