Progress in identifying peptides and small-molecule inhibitors targeted to gp41 of HIV-1
- 24 April 2006
- journal article
- review article
- Published by Informa Healthcare in Expert Opinion on Investigational Drugs
- Vol. 15 (5), 465-478
- https://doi.org/10.1517/13543784.15.5.465
Abstract
During the last decade, a great number of activities have been geared in identifying newer targets for inhibiting HIV infection as well as understanding the targets for already identified anti-HIV-1 agents. The success in converting a proof-of-concept peptide T-20 (previously named DP-178), from the C-terminal heptad repeat (CHR) region of the envelope glycoprotein gp41 of HIV-1, to a drug named enfuvirtide was one of the phenomenal successes in HIV-1 drug discovery research that has been made in recent years. There were many reports of modifying peptides from the N-terminal heptad repeat and CHR regions with the objective of improving their activity. A few laboratories also reported the identification of small-molecule inhibitors that apparently bind to the hydrophobic cavity identified in the gp41 core structure and prevent the CHR peptide binding to the N-terminal heptad repeat peptide, thereby prevent the formation of the typical six-helix bundle, which has been thought to be necessary for the fusion between HIV and cell membranes.Keywords
This publication has 53 references indexed in Scilit:
- Rational design of highly potent HIV-1 fusion inhibitory proteins: Implication for developing antiviral therapeuticsBiochemical and Biophysical Research Communications, 2005
- Differential Inhibition of HIV-1 and SIV Envelope-Mediated Cell Fusion by C34 Peptides Derived from the C-Terminal Heptad Repeat of gp41 from Diverse Strains of HIV-1, HIV-2, and SIVJournal of Medicinal Chemistry, 2005
- XTT Formazan Widely Used to Detect Cell Viability Inhibits HIV Type 1 Infectionin Vitroby Targeting gp41AIDS Research and Human Retroviruses, 2002
- The Safety, Plasma Pharmacokinetics, and Antiviral Activity of Subcutaneous Enfuvirtide (T-20), a Peptide Inhibitor of gp41-Mediated Virus Fusion, in HIV-Infected AdultsAIDS Research and Human Retroviruses, 2002
- Design of a Protein Surface Antagonist Based on α-Helix Mimicry: Inhibition of gp41 Assembly and Viral Fusion We thank the National Institutes of Health for support of this work and the Deutsche Forschungsgemeinschaft (DFG) for a research fellowship to O.K.Angewandte Chemie, 2002
- A Salt Bridge between an N-terminal Coiled Coil of gp41 and an Antiviral Agent Targeted to the gp41 Core Is Important for Anti-HIV-1 ActivityBiochemical and Biophysical Research Communications, 2000
- Development of HIV Entry Inhibitors Targeted to the Coiled-Coil Regions of gp41Biochemical and Biophysical Research Communications, 2000
- Structure-Based Identification of Small Molecule Antiviral Compounds Targeted to the gp41 Core Structure of the Human Immunodeficiency Virus Type 1Journal of Medicinal Chemistry, 1999
- Crystal structure of GCN4-pIQI, a trimeric coiled coil with buried polar residuesJournal of Molecular Biology, 1998
- A Synthetic Peptide from HIV-1 gp41 Is a Potent Inhibitor of Virus-Mediated Cell—Cell FusionAIDS Research and Human Retroviruses, 1993