基于点击化学的双组分系统用于高效抑制人类免疫缺陷病毒（HIV）逆转录酶（RT）

Ledezma Carlos E, Cornett Evan M, Kolpashchikov Dmitry M

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

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

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.

我们合成了两种用于在DNA聚合酶活性位点进行无铜“点击”化学偶联的dTTP类似物。我们发现，在两种类似物都存在的情况下，人类免疫缺陷病毒（HIV）逆转录酶（RT）的活性被抑制高达93%。与传统的HIV RT抑制剂叠氮胸苷不同，过量的引物模板并不能恢复这种抑制作用。这一发现可能成为开发高效的HIV RT体内抑制剂及其他DNA聚合酶抑制剂的基础。