Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, Quebec H3A 0B8, Canada.
Department of Biochemistry, McGill University, 3655 Sir William Osler Promenade, Montreal, Quebec H3G1Y6, Canada.
Bioorg Med Chem. 2018 May 1;26(8):1713-1726. doi: 10.1016/j.bmc.2018.02.017. Epub 2018 Feb 14.
Reverse transcriptase (RT) is responsible for replicating the HIV-1 genome and is a validated therapeutic target for the treatment of HIV infections. During each cycle of the RT-catalyzed DNA polymerization process, inorganic pyrophosphate is released as the by-product of nucleotide incorporation. Small molecules were identified that act as bioisosteres of pyrophosphate and can selectively freeze the catalytic cycle of HIV-1 RT at the pre-translocated stage of the DNA- or RNA-template-primer-enzyme complex.
逆转录酶（RT）负责复制 HIV-1 基因组，是治疗 HIV 感染的有效治疗靶点。在 RT 催化的 DNA 聚合过程的每个循环中，无机焦磷酸作为核苷酸掺入的副产物释放。已经鉴定出一些小分子，它们是焦磷酸盐的生物等排体，可以选择性地将 HIV-1 RT 的催化循环在 DNA 或 RNA 模板-引物-酶复合物的预转移阶段冻结。
