PMID: 10520998Oct 16, 1999Paper

Inhibiting HIV-1 entry: discovery of D-peptide inhibitors that target the gp41 coiled-coil pocket

D M EckertP S Kim


The HIV-1 gp41 protein promotes viral entry by mediating the fusion of viral and cellular membranes. A prominent pocket on the surface of a central trimeric coiled coil within gp41 was previously identified as a potential target for drugs that inhibit HIV-1 entry. We designed a peptide, IQN17, which properly presents this pocket. Utilizing IQN17 and mirror-image phage display, we identified cyclic, D-peptide inhibitors of HIV-1 infection that share a sequence motif. A 1.5 A cocrystal structure of IQN17 in complex with a D-peptide, and NMR studies, show that conserved residues of these inhibitors make intimate contact with the gp41 pocket. Our studies validate the pocket per se as a target for drug development. IQN17 and these D-peptide inhibitors are likely to be useful for development and identification of a new class of orally bioavailable anti-HIV drugs.


May 17, 2000·The Journal of General Virology·J Schneider-Schaulies
Jun 20, 2001·Nature Reviews. Molecular Cell Biology·J P Moore, M Stevenson
Feb 15, 2001·Current Infectious Disease Reports·Georgia D. Tomaras, Michael L. Greenberg
Jun 8, 2001·Annual Review of Biochemistry·D M Eckert, P S Kim
Jan 24, 2002·AIDS Research and Human Retroviruses·Julià BlancoJosé A Esté
Jan 4, 2003·Chembiochem : a European Journal of Chemical Biology·Sachdev S SidhuKurt Deshayes
Sep 10, 2003·Chembiochem : a European Journal of Chemical Biology·Katja Wiesehan, Dieter Willbold
Jul 2, 2005·Expert Opinion on Emerging Drugs·S Redshaw, M Westby
Aug 30, 2005·Antimicrobial Agents and Chemotherapy·Julià BlancoJosé A Esté
Sep 1, 2005·Proceedings of the National Academy of Sciences of the United States of America·Elisabetta BianchiAntonello Pessi
Sep 16, 2006·The FEBS Journal·Zhiyong LouZihe Rao
Oct 17, 2007·Chemical Biology & Drug Design·Weiming Xu, John W Taylor
Nov 29, 2007·Proceedings of the National Academy of Sciences of the United States of America·Feng ZhouYi Li
Mar 25, 2008·Protein Science : a Publication of the Protein Society·John J DwyerMary K Delmedico
Jun 12, 2008·Macromolecular Bioscience·Zhongli LuoShuguang Zhang
Aug 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·W Seth HorneSamuel H Gellman
May 21, 2010·Proceedings of the National Academy of Sciences of the United States of America·Elisabetta BianchiPeter S Kim
Dec 17, 2010·AIDS Research and Human Retroviruses·Bimal K ChakrabartiRichard T Wyatt
Jul 16, 2010·Journal of Peptide Science : an Official Publication of the European Peptide Society·Rong Jian LuBrian Bray
Jul 9, 2011·Protein Science : a Publication of the Protein Society·Joseph S HarrisonJonathan R Lai
Apr 28, 2011·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Guillaume CastelNoël Tordo
May 19, 2012·International Journal of Molecular Sciences·Sylvie DelhalleAndy Chevigné
Jul 31, 2013·Journal of Computer-aided Molecular Design·Miriam GochinDale L Boger
Nov 28, 2014·Expert Opinion on Therapeutic Patents·Dongmei ZhangShibo Jiang
Oct 8, 2014·Protein Science : a Publication of the Protein Society·Tracy R ClintonMichael S Kay
May 21, 2016·Chemical Communications : Chem Comm·Taro NoguchiNobutaka Fujii
Mar 15, 2018·Frontiers in Cellular and Infection Microbiology·Xiujuan ZhangYuxian He
Jul 4, 2019·Chembiochem : a European Journal of Chemical Biology·Cristina Díaz-PerlasErnest Giralt
Aug 14, 2020·International Journal of Molecular Sciences·Rolando CannalireVincenzo Summa
Mar 13, 2001·Annual Review of Immunology·P PoignardD R Burton

❮ Previous
Next ❯

Related Concepts

Related Feeds

BioHub - Researcher Network

The Chan-Zuckerberg Biohub aims to support the fundamental research and develop the technologies that will enable physicians to cure, prevent, or manage all diseases in our childrens' lifetimes. The CZ Biohub brings together researchers from UC Berkeley, Stanford, and UCSF. Find the latest research from the CZ Biohub researcher network here.

Cell eTOC

Cell is a scientific journal publishing research across a broad range of disciplines within the life sciences field. Discover the latest research from Cell here.