Literature DB >> 33956029

A targeted covalent small molecule inhibitor of HIV-1 fusion.

Guangyan Zhou1, Li He1, Kathy H Li2, Cássio C S Pedroso3, Miriam Gochin4.   

Abstract

We describe a low molecular weight covalent inhibitor targeting a conserved lysine residue within the hydrophobic pocket of HIV-1 glycoprotein-41. The inhibitor bound selectively to the hydrophobic pocket and exhibited an order of magnitude enhancement of anti-fusion activity against HIV-1 compared to its non-covalent counterpart. The findings represent a significant advance in the quest to obtain non-peptide fusion inhibitors.

Entities:  

Mesh：

Substances：

Year:  2021        PMID： 33956029      PMCID： PMC8141304          DOI： 10.1039/d1cc01013a

Source DB:  PubMed          Journal:  Chem Commun (Camb)        ISSN： 1359-7345            Impact factor:   6.222


  37 in total

1.  Selection with a peptide fusion inhibitor corresponding to the first heptad repeat of HIV-1 gp41 identifies two genetic pathways conferring cross-resistance to peptide fusion inhibitors corresponding to the first and second heptad repeats (HR1 and HR2) of gp41.

Authors:  Wei Wang; Christopher J De Feo; Min Zhuang; Russell Vassell; Carol D Weiss
Journal:  J Virol       Date:  2011-10-12       Impact factor: 5.103

2.  Evidence that a prominent cavity in the coiled coil of HIV type 1 gp41 is an attractive drug target.

Authors:  D C Chan; C T Chutkowski; P S Kim
Journal:  Proc Natl Acad Sci U S A       Date:  1998-12-22       Impact factor: 11.205

Review 3.  The resurgence of covalent drugs.

Authors:  Juswinder Singh; Russell C Petter; Thomas A Baillie; Adrian Whitty
Journal:  Nat Rev Drug Discov       Date:  2011-04       Impact factor: 84.694

4.  Design and characterization of swapped-domain constructs of HIV-1 glycoprotein-41 as receptors for drug discovery.

Authors:  Joseph D Walsh; Shidong Chu; Shao-Qing Zhang; Miriam Gochin
Journal:  Protein Eng Des Sel       Date:  2015-04       Impact factor: 1.650

5.  Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy.

Authors:  Xiping Wei; Julie M Decker; Hongmei Liu; Zee Zhang; Ramin B Arani; J Michael Kilby; Michael S Saag; Xiaoyun Wu; George M Shaw; John C Kappes
Journal:  Antimicrob Agents Chemother       Date:  2002-06       Impact factor: 5.191

6.  Covalent fusion inhibitors targeting HIV-1 gp41 deep pocket.

Authors:  Yu Bai; Huifang Xue; Kun Wang; Lifeng Cai; Jiayin Qiu; Shuangyu Bi; Luhua Lai; Maosheng Cheng; Shuwen Liu; Keliang Liu
Journal:  Amino Acids       Date:  2012-09-09       Impact factor: 3.520

7.  The role of amphiphilicity and negative charge in glycoprotein 41 interactions in the hydrophobic pocket.

Authors:  Miriam Gochin; Lifeng Cai
Journal:  J Med Chem       Date:  2009-07-23       Impact factor: 7.446

8.  Structure-activity relationship studies of indole-based compounds as small molecule HIV-1 fusion inhibitors targeting glycoprotein 41.

Authors:  Guangyan Zhou; Vladimir Sofiyev; Hardeep Kaur; Beth A Snyder; Marie K Mankowski; Priscilla A Hogan; Roger G Ptak; Miriam Gochin
Journal:  J Med Chem       Date:  2014-06-06       Impact factor: 7.446

Review 9.  Lysine-Targeting Covalent Inhibitors.

Authors:  Jonathan Pettinger; Keith Jones; Matthew D Cheeseman
Journal:  Angew Chem Int Ed Engl       Date:  2017-10-27       Impact factor: 15.336

10.  Computer-Aided Approaches for Targeting HIVgp41.

Authors:  William J Allen; Robert C Rizzo
Journal:  Biology (Basel)       Date:  2012-08-20
View more

北京卡尤迪生物科技股份有限公司 © 2022-2023.