Triazinylamidophosphate Oligonucleotides: Synthesis and Study of Their Interaction with Cells and DNA-Binding Proteins

M. S. Kupryushkin, T. D. Zharkov, E. S. Ilina, O. V. Markov, A. S. Kochetkova, M. M. Akhmetova, A. A. Lomzov, D. V. Pyshnyi, O. I. Lavrik, S. N. Khodyreva

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)719-733
Number of pages15
JournalRussian Journal of Bioorganic Chemistry
Volume47
Issue number3
DOIs
Publication statusPublished - May 2021

Keywords

  • automated amidophosphite synthesis
  • Ku-antigen
  • PARP1
  • Staudinger’s reaction
  • triazinylamidophosphate oligonucleotides

OECD FOS+WOS

  • 1.06 BIOLOGICAL SCIENCES
  • 1.04 CHEMICAL SCIENCES
  • 1.06.CQ BIOCHEMISTRY & MOLECULAR BIOLOGY

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