Abstract

In this work, representatives of the class of triazinylamidophosphate oligonucleotide derivatives were obtained for the first time. A scheme for the introduction of a modified unit on a solid-phase support during the oxidation step with highly reactive 2-azido-4,6-dichloro[1,3,5]triazine according to the Staudinger reaction was proposed and implemented, followed by the introduction of various aliphatic residues upon treatment with the corresponding amines. A number of model oligonucleotides containing triazinylamidophosphate modification were synthesized. Chemical stability, cellular uptake, and cytotoxicity of the obtained derivatives were studied. The effect of the type of aliphatic substituent in the composition of the oligonucleotides obtained on their resistance to enzymatic hydrolysis in extracts of cultured human cells with different contents of key DNA repair regulatory proteins, Ku-antigen and poly(ADP-ribose) polymerase 1 (PARP1), which are potentially the most effective acceptors of modified oligonucleotides, was studied.

中文翻译：

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Triazinyamidophosphate 寡核苷酸：它们与细胞和 DNA 结合蛋白相互作用的合成和研究

摘要

在这项工作中，首次获得了三嗪基氨基磷酸酯寡核苷酸衍生物类的代表。提出并实施了根据施陶丁格反应在氧化步骤中在固相载体上引入修饰单元与高反应性 2-叠氮基-4,6-二氯[1,3,5]三嗪的方案，然后通过在用相应的胺处理后引入各种脂肪族残基。合成了许多含有三嗪基氨基磷酸酯修饰的模型寡核苷酸。研究了所得衍生物的化学稳定性、细胞摄取和细胞毒性。