Zharkov, T.D.; Markov, O.V.; Zhukov, S.A.; Khodyreva, S.N.; Kupryushkin, M.S. Influence of Combinations of Lipophilic and Phosphate Backbone Modifications on Cellular Uptake of Modified Oligonucleotides. Molecules2024, 29, 452.
Zharkov, T.D.; Markov, O.V.; Zhukov, S.A.; Khodyreva, S.N.; Kupryushkin, M.S. Influence of Combinations of Lipophilic and Phosphate Backbone Modifications on Cellular Uptake of Modified Oligonucleotides. Molecules 2024, 29, 452.
Zharkov, T.D.; Markov, O.V.; Zhukov, S.A.; Khodyreva, S.N.; Kupryushkin, M.S. Influence of Combinations of Lipophilic and Phosphate Backbone Modifications on Cellular Uptake of Modified Oligonucleotides. Molecules2024, 29, 452.
Zharkov, T.D.; Markov, O.V.; Zhukov, S.A.; Khodyreva, S.N.; Kupryushkin, M.S. Influence of Combinations of Lipophilic and Phosphate Backbone Modifications on Cellular Uptake of Modified Oligonucleotides. Molecules 2024, 29, 452.
Abstract
Numerous types of oligonucleotide modifications have been developed since automated synthesis of DNA/RNA became a common instrument in the creation of synthetic oligonucleotides. Despite the growing number of types of oligonucleotide modifications under development, only a few of them, and moreover, their combinations have been studied wide enough in terms of their in-fluence on the properties of corresponding NA constructions. In the present study, a number of oligonucleotides with combinations of 3′ end lipophilic (single cholesteryl or pair of dodecyl residues) and phosphate backbone modifications were synthesized. The influence of the combi-nation of used lipophilic groups with phosphate modifications of various nature and different position on the efficiency of cell penetration was evaluated. Obtained results indicate that even a couple of phosphate modifications are able to affect a set of oligonucleotide properties in a complex manner and can remarkably change cellular uptake. These data clearly show that the strategy of using different patterns of modification combinations has great potential for the ra-tional design of oligonucleotide structures with desired predefined properties.
Chemistry and Materials Science, Medicinal Chemistry
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