Kuznetsova E V, Kukhanova M K, Gurskaia G V, Fedorov I I, Ias'ko M V, Chattopadiiyaya J, Kraevskiĭ A A
University of Uppsala, Sweden.
Mol Biol (Mosk). 1995 Mar-Apr;29(2):407-14.
The structure of new nucleoside--3'-nitro-2',3'-dideoxythymidine (NIT) possessing moderate anti HIV activity in MT-4 cell culture was investigated by X-ray analysis. These data showed that conformation of NIT in crystal is similar to that of one of crystallographically independent forms of 3'-azido-2',3'-dideoxythymidine. 3'-Nitro-2',3'-dideoxythymidine 5'-triphosphate (NITTP) was synthesized and its ability to inhibit human and viral DNA polymerases was studied. NITTP proved to be effective and highly selective terminating substrate of DNA synthesis catalyzed by HIV and AMV reverse transcriptases. Human DNA polymerase alpha as well as DNA polymerase beta (rat liver), terminal deoxynucleotidyltransferase (calf thymus) or HSV-1 and CMV DNA polymerases did not incorporate NITTP into a growing DNA chain.
通过X射线分析研究了在MT-4细胞培养中具有中等抗HIV活性的新型核苷——3'-硝基-2',3'-双脱氧胸苷（NIT）的结构。这些数据表明，NIT在晶体中的构象与3'-叠氮基-2',3'-双脱氧胸苷的一种晶体学独立形式的构象相似。合成了3'-硝基-2',3'-双脱氧胸苷5'-三磷酸酯（NITTP），并研究了其抑制人及病毒DNA聚合酶的能力。NITTP被证明是HIV和AMV逆转录酶催化的DNA合成的有效且高度选择性的终止底物。人DNA聚合酶α以及DNA聚合酶β（大鼠肝脏）、末端脱氧核苷酸转移酶（小牛胸腺）或HSV-1和CMV DNA聚合酶均未将NITTP掺入正在延长的DNA链中。
