Macrocyclic Envelope Glycoprotein Antagonists that Irreversibly Inactivate HIV-1 before Host Cell Encounter

Adel A Rashad; Ramalingam Venkat Kalyana Sundaram; Rachna Aneja; Caitlin Duffy; Irwin Chaiken

doi:10.1021/acs.jmedchem.5b00935

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Macrocyclic Envelope Glycoprotein Antagonists that Irreversibly Inactivate HIV-1 before Host Cell Encounter

Journal article

Open access

Peer reviewed

Macrocyclic Envelope Glycoprotein Antagonists that Irreversibly Inactivate HIV-1 before Host Cell Encounter

Adel A Rashad, Ramalingam Venkat Kalyana Sundaram, Rachna Aneja, Caitlin Duffy and Irwin Chaiken

Journal of medicinal chemistry, v 58(18), pp 7603-7608

24 Sep 2015

DOI: https://doi.org/10.1021/acs.jmedchem.5b00935

PMID: 26331669

Featured in Collection : UN Sustainable Development Goals @ Drexel

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Abstract

Anti-HIV Agents - chemical synthesis

Anti-HIV Agents - chemistry

Anti-HIV Agents - pharmacology

Cell Line

Chymotrypsin - chemistry

HIV Envelope Protein gp120 - antagonists & inhibitors

HIV-1 - drug effects

HIV-1 - physiology

Humans

Models, Molecular

Oligopeptides - chemical synthesis

Oligopeptides - chemistry

Oligopeptides - pharmacology

Peptides, Cyclic - chemical synthesis

Peptides, Cyclic - chemistry

Peptides, Cyclic - pharmacology

Protein Conformation

Triazoles - chemical synthesis

Triazoles - chemistry

Triazoles - pharmacology

Trypsin - chemistry

Virion - drug effects

Virion - physiology

Virus Internalization

We derived macrocyclic HIV-1 antagonists as a new class of peptidomimetic drug leads. Cyclic peptide triazoles (cPTs) retained the gp120 inhibitory and virus-inactivating signature of parent PTs, arguing that cyclization locked an active conformation. The six-residue cPT 9 (AAR029b) exhibited submicromolar antiviral potencies in inhibiting cell infection and triggering gp120 shedding that causes irreversible virion inactivation. Importantly, cPTs were stable to trypsin and chymotrypsin compared to substantial susceptibility of corresponding linear PTs.

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30 citations in Scopus

Details

Title: Macrocyclic Envelope Glycoprotein Antagonists that Irreversibly Inactivate HIV-1 before Host Cell Encounter
Creators: Adel A Rashad - Drexel University
Ramalingam Venkat Kalyana Sundaram - School of Biomedical Engineering, Science and Health Systems, Drexel University , Philadelphia, Pennsylvania 19104 United States
Rachna Aneja - Drexel University
Caitlin Duffy - Drexel University
Irwin Chaiken - Drexel University
Publication Details: Journal of medicinal chemistry, v 58(18), pp 7603-7608
Publisher: American Chemical Society; Washington, DC
Grant note: P01 GM056550 / NIGMS NIH HHS GM 56550-17 / NIGMS NIH HHS
Resource Type: Journal article
Language: English
Academic Unit: Biochemistry and Molecular Biology; Thomas R. Kline School of Law
Web of Science ID: WOS:000361921800039
Scopus ID: 2-s2.0-84942279944
Other Identifier: 991019168409004721

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Web of Science research areas: Chemistry, Medicinal

Macrocyclic Envelope Glycoprotein Antagonists that Irreversibly Inactivate HIV-1 before Host Cell Encounter

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Abstract

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UN Sustainable Development Goals (SDGs)

InCites Highlights

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