Click Chemistry-Based Two-Component System for Efficient Inhibition of Human Immunodeficiency Virus (HIV) Reverse Transcriptase (RT)

[Image: see text] We synthesized two dTTP analogues for copper-free “click” chemistry-coupling in the active sites of DNA polymerases. We found that in the presence of both analogues, human immunodeficiency virus (HIV) reverse transcriptase (RT) activity was suppressed by up to 93%. This inhibitory...

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Autores principales: Ledezma, Carlos E., Cornett, Evan M., Kolpashchikov, Dmitry M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2020
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057708/
https://www.ncbi.nlm.nih.gov/pubmed/32149246
http://dx.doi.org/10.1021/acsomega.9b03942
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author Ledezma, Carlos E.
Cornett, Evan M.
Kolpashchikov, Dmitry M.
author_facet Ledezma, Carlos E.
Cornett, Evan M.
Kolpashchikov, Dmitry M.
author_sort Ledezma, Carlos E.
collection PubMed
description [Image: see text] We synthesized two dTTP analogues for copper-free “click” chemistry-coupling in the active sites of DNA polymerases. We found that in the presence of both analogues, human immunodeficiency virus (HIV) reverse transcriptase (RT) activity was suppressed by up to 93%. This inhibitory effect was not recovered by an excess amount of primer–template unlike that for a conventional HIV RT inhibitor, azidothymidine. This finding may become the basis for the development of efficient in vivo inhibitors of HIV RT and other DNA polymerases.
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spelling pubmed-70577082020-03-06 Click Chemistry-Based Two-Component System for Efficient Inhibition of Human Immunodeficiency Virus (HIV) Reverse Transcriptase (RT) Ledezma, Carlos E. Cornett, Evan M. Kolpashchikov, Dmitry M. ACS Omega [Image: see text] We synthesized two dTTP analogues for copper-free “click” chemistry-coupling in the active sites of DNA polymerases. We found that in the presence of both analogues, human immunodeficiency virus (HIV) reverse transcriptase (RT) activity was suppressed by up to 93%. This inhibitory effect was not recovered by an excess amount of primer–template unlike that for a conventional HIV RT inhibitor, azidothymidine. This finding may become the basis for the development of efficient in vivo inhibitors of HIV RT and other DNA polymerases. American Chemical Society 2020-02-21 /pmc/articles/PMC7057708/ /pubmed/32149246 http://dx.doi.org/10.1021/acsomega.9b03942 Text en Copyright © 2020 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Ledezma, Carlos E.
Cornett, Evan M.
Kolpashchikov, Dmitry M.
Click Chemistry-Based Two-Component System for Efficient Inhibition of Human Immunodeficiency Virus (HIV) Reverse Transcriptase (RT)
title Click Chemistry-Based Two-Component System for Efficient Inhibition of Human Immunodeficiency Virus (HIV) Reverse Transcriptase (RT)
title_full Click Chemistry-Based Two-Component System for Efficient Inhibition of Human Immunodeficiency Virus (HIV) Reverse Transcriptase (RT)
title_fullStr Click Chemistry-Based Two-Component System for Efficient Inhibition of Human Immunodeficiency Virus (HIV) Reverse Transcriptase (RT)
title_full_unstemmed Click Chemistry-Based Two-Component System for Efficient Inhibition of Human Immunodeficiency Virus (HIV) Reverse Transcriptase (RT)
title_short Click Chemistry-Based Two-Component System for Efficient Inhibition of Human Immunodeficiency Virus (HIV) Reverse Transcriptase (RT)
title_sort click chemistry-based two-component system for efficient inhibition of human immunodeficiency virus (hiv) reverse transcriptase (rt)
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057708/
https://www.ncbi.nlm.nih.gov/pubmed/32149246
http://dx.doi.org/10.1021/acsomega.9b03942
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