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

Carlos E Ledezma; Evan M Cornett; Dmitry M Kolpashchikov

doi:10.1021/acsomega.9b03942

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

ACS Omega. 2020 Feb 21;5(8):4167-4171. doi: 10.1021/acsomega.9b03942. eCollection 2020 Mar 3.

Authors

Carlos E Ledezma¹, Evan M Cornett¹, Dmitry M Kolpashchikov¹

Affiliation

¹ Department of Chemistry, University of Central Florida, 4111 Libra Drive, Orlando, Florida 32816, United States.

Abstract

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.