Literature DB >> 23380374

Bifunctional inhibition of HIV-1 reverse transcriptase: a first step in designing a bifunctional triphosphate.

Dongyuan Piao1, Aravind Basavapathruni, Pinar Iyidogan, Guangxiu Dai, Wolfgang Hinz, Adrian S Ray, Eisuke Murakami, Joy Y Feng, Fei You, Ginger E Dutschman, David J Austin, Kathlyn A Parker, Karen S Anderson.   

Abstract

The onset of resistance to approved anti-AIDS drugs by HIV necessitates the search for novel inhibitors of HIV-1 reverse transcriptase (RT). Developing single molecular agents concurrently occupying the nucleoside and nonnucleoside binding sites in RT is an intriguing idea but the proof of concept has so far been elusive. As a first step, we describe molecular modeling to guide focused chemical syntheses of conjugates having nucleoside (d4T) and nonnucleoside (TIBO) moieties tethered by a flexible polyethylene glycol (PEG) linker. A triphosphate of d4T-6PEG-TIBO conjugate was successfully synthesized that is recognized as a substrate by HIV-1 RT and incorporated into a double-stranded DNA.
Copyright © 2013 Elsevier Ltd. All rights reserved.

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Year:  2012        PMID： 23380374      PMCID： PMC3580853          DOI： 10.1016/j.bmcl.2012.12.015

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  38 in total

Review 1.  Factors contributing to the inhibition of HIV reverse transcriptase by chain-terminating nucleotides in vitro and in vivo.

Authors:  R S Goody; B Müller; T Restle
Journal:  FEBS Lett       Date:  1991-10-07       Impact factor: 4.124

2.  Synthesis and anti-HIV activity of [d4U]-[trovirdine analogue] and [d4T]-[trovirdine analogue] heterodimers as inhibitors of HIV-1 reverse transcriptase.

Authors:  D Gavriliu; C Fossey; A Ciurea; Z Delbederi; E Sugeac; D Ladurée; S Schmidt; G Laumond; A M Aubertin
Journal:  Nucleosides Nucleotides Nucleic Acids       Date:  2002       Impact factor: 1.381

3.  Kinetic interaction of human immunodeficiency virus type 1 reverse transcriptase with the antiviral tetrahydroimidazo[4,5,1-jk]-[1,4]-benzodiazepine-2-(1H)-thione compound, R82150.

Authors:  K B Frank; G J Noll; E V Connell; I S Sim
Journal:  J Biol Chem       Date:  1991-08-05       Impact factor: 5.157

4.  An antiviral target on reverse transcriptase of human immunodeficiency virus type 1 revealed by tetrahydroimidazo-[4,5,1-jk] [1,4]benzodiazepin-2 (1H)-one and -thione derivatives.

Authors:  Z Debyser; R Pauwels; K Andries; J Desmyter; M Kukla; P A Janssen; E De Clercq
Journal:  Proc Natl Acad Sci U S A       Date:  1991-02-15       Impact factor: 11.205

5.  Inhibition of HIV-1 replication by a nonnucleoside reverse transcriptase inhibitor.

Authors:  V J Merluzzi; K D Hargrave; M Labadia; K Grozinger; M Skoog; J C Wu; C K Shih; K Eckner; S Hattox; J Adams
Journal:  Science       Date:  1990-12-07       Impact factor: 47.728

6.  A novel mechanism for inhibition of HIV-1 reverse transcriptase.

Authors:  A Geoffrey Skillman; Karl W Maurer; Diana C Roe; Margaret J Stauber; Dolan Eargle; Todd J A Ewing; Angelika Muscate; Elisabeth Davioud-Charvet; Maxine V Medaglia; Robert J Fisher; Edward Arnold; Hong Qiang Gao; Robert Buckheit; Paul L Boyer; Stephen H Hughes; Irwin D Kuntz; George L Kenyon
Journal:  Bioorg Chem       Date:  2002-12       Impact factor: 5.275

7.  Defining a molecular mechanism of synergy between nucleoside and nonnucleoside AIDS drugs.

Authors:  Aravind Basavapathruni; Christopher M Bailey; Karen S Anderson
Journal:  J Biol Chem       Date:  2004-01-13       Impact factor: 5.157

8.  Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor.

Authors:  L A Kohlstaedt; J Wang; J M Friedman; P A Rice; T A Steitz
Journal:  Science       Date:  1992-06-26       Impact factor: 47.728

9.  Inhibition of HIV-1 reverse transcriptase by pyridinone derivatives. Potency, binding characteristics, and effect of template sequence.

Authors:  S S Carroll; D B Olsen; C D Bennett; L Gotlib; D J Graham; J H Condra; A M Stern; J A Shafer; L C Kuo
Journal:  J Biol Chem       Date:  1993-01-05       Impact factor: 5.157

10.  Cellular pharmacology of 2',3'-dideoxy-2',3'-didehydrothymidine, a nucleoside analog active against human immunodeficiency virus.

Authors:  H T Ho; M J Hitchcock
Journal:  Antimicrob Agents Chemother       Date:  1989-06       Impact factor: 5.938
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  2 in total

1.  Bifunctional inhibition of human immunodeficiency virus type 1 reverse transcriptase: mechanism and proof-of-concept as a novel therapeutic design strategy.

Authors:  Christopher M Bailey; Todd J Sullivan; Pinar Iyidogan; Julian Tirado-Rives; Raymond Chung; Juliana Ruiz-Caro; Ebrahim Mohamed; William L Jorgensen; William Jorgensen; Roger Hunter; Karen S Anderson
Journal:  J Med Chem       Date:  2013-05-09       Impact factor: 7.446

2.  Design, Synthesis, and Antiviral Evaluation of Chimeric Inhibitors of HIV Reverse Transcriptase.

Authors:  Pinar Iyidogan; Todd J Sullivan; Mahendra D Chordia; Kathleen M Frey; Karen S Anderson
Journal:  ACS Med Chem Lett       Date:  2013-10-15       Impact factor: 4.345
  2 in total

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