Research output: Contribution to journal › Article › peer-review
Triazinylamidophosphate Oligonucleotides : Synthesis and Study of Their Interaction with Cells and DNA-Binding Proteins. / Kupryushkin, M. S.; Zharkov, T. D.; Ilina, E. S. et al.
In: Russian Journal of Bioorganic Chemistry, Vol. 47, No. 3, 05.2021, p. 719-733.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Triazinylamidophosphate Oligonucleotides
T2 - Synthesis and Study of Their Interaction with Cells and DNA-Binding Proteins
AU - Kupryushkin, M. S.
AU - Zharkov, T. D.
AU - Ilina, E. S.
AU - Markov, O. V.
AU - Kochetkova, A. S.
AU - Akhmetova, M. M.
AU - Lomzov, A. A.
AU - Pyshnyi, D. V.
AU - Lavrik, O. I.
AU - Khodyreva, S. N.
N1 - Funding Information: The work was supported by the Russian Science Foundation (project no. 19-14-00204). Publisher Copyright: © 2021, Pleiades Publishing, Ltd. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/5
Y1 - 2021/5
N2 - 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.
AB - 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.
KW - automated amidophosphite synthesis
KW - Ku-antigen
KW - PARP1
KW - Staudinger’s reaction
KW - triazinylamidophosphate oligonucleotides
UR - http://www.scopus.com/inward/record.url?scp=85107601697&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/0240e158-69d9-3ce2-b7e0-8939918d7a16/
U2 - 10.1134/S1068162021030110
DO - 10.1134/S1068162021030110
M3 - Article
AN - SCOPUS:85107601697
VL - 47
SP - 719
EP - 733
JO - Russian Journal of Bioorganic Chemistry
JF - Russian Journal of Bioorganic Chemistry
SN - 1068-1620
IS - 3
ER -
ID: 28918889