vestichИзвестия Национальной академии наук Беларуси. Серия химических наукProceedings of the National Academy of Sciences of Belarus, Chemical Series1561-83312524-2342The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1561-8331-2018-54-1-46-57vestich-303Research ArticleОРГАНИЧЕСКАЯ ХИМИЯORGANIC CHEMISTRYСИНТЕЗ КОНЪЮГАТОВ ОЛИГОНУКЛЕОТИДОВ С ПРОИЗВОДНЫМИ 11,11-D2-ЛИНОЛЕВОЙ КИСЛОТЫ ПО РЕАКЦИИ АЗИД-АЛКИНОВОГО ЦИКЛОПРИСОЕДИНЕНИЯSYNTHESIS OF CONJUGATES OF OLIGONUCLEOTIDES AND 11,11-D2-LINOLEIC ACID DERIVATIVES VIA AZIDE-ALKYNE CYCLOADDITIONФомичМ. А.FomichM. A.

науч. сотрудник

ул. Сурганова, 13, 220072, Минск

Researcher

13, Surganov Str., 220072, Minsk

mfomich@gmail.comБекишА. В.BekishA. V.

канд. хим. наук, доцент

ул. Ленин- градская, 14, 220030, Минск

Ph. D. (Chemistry), Associate Professor

14, Leningradskaya Str., 220030, Minsk

andreibekish@yahoo.comШаркоО. Л.SharkoO. L.

канд. хим. наук, ст. науч. сотрудник

ул. Сурганова, 13, 220072, Минск

Ph. D. (Chemistry), Senior Researcher

13, Surganov Str., 220072, Minsk

sharko@ifoch.bas-net.byПрохоревичК. Н.ProkhorevichK. N.

канд. хим. наук, доцент

пр. Независимости, 220, 220057, Минск

Ph. D. (Chemistry), Associate Professor

220, Nezavisimosti Ave., 220057, Minsk

kprokhorevich@yahoo.comШманайВ. В.ShmanaiV. V.

канд. хим. наук, зав. лаб. химии биоконъюгатов

ул. Сурганова, 13, 220072, Минск

Ph. D. (Chemistry), Head of the Laboratory of Bioconjugate Chemistry

13, Surganov Str., 220072, Minsk

shmanai@ifoch.bas-net.byИнститут физико-органической химии Национальной академии наук БеларусиInstitute of Physical Organic Chemistry of the National Academy of Sciences of BelarusБелорусский государственный университетBelarusian State UniversityВоенная академия Республики БеларусьBelarusian Military Academy2018050320185414657Copyright © Фомич М.А., Бекиш А.В., Шарко О.Л., Прохоревич К.Н., Шманай В.В., 20182018Фомич М.А., Бекиш А.В., Шарко О.Л., Прохоревич К.Н., Шманай В.В.Fomich M.A., Bekish A.V., Sharko O.L., Prokhorevich K.N., Shmanai V.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestichem.belnauka.by/jour/article/view/303

Предложен новый подход к синтезу конъюгатов олигонуклеотидов и жирных кислот, основанный на медь-катализируемой реакции циклоприсоединения азидсодержащих олигонуклеотидов к производным жирных кислот с терминальной тройной связью (CuAAC). Для демонстрации этого подхода осуществлен синтез пяти производных 11,11-D2-линолевой кислоты, содержащих концевую тройную связь в различных частях молекулы. Разработана методика их конъюгации с азидсодержащим модельным олигонуклеотидом Т20, проверено влияние различных условий (времени, концентрации катализатора, избытка алкинсодержащего реагента, состава растворителя и др.) на выход продукта. Такие конъюгаты устойчивы в биологических средах, обладают повышенной способностью проникать в клетки и могут найти применение в качестве средств генной терапии. 

A new approach to the synthesis of oligonucleotide-fatty acid conjugates is reported. It is based on Cu-catalyzed reaction between azide oligonucleotides and fatty acid derivatives with terminal triple bond (CuAAC). To demonstrate this approach, five derivatives of 11,11-D2-linoleic acid containing terminal alkyne group at different parts of the molecule were synthesized. A method of conjugation of alkyne 11,11-D2-linoleic acid with azide oligonucleotide T20 is developed, and the conditions (time, concentration of Cu catalyst, excess of alkyne reagent, composition of the solvent, etc.) are optimized. These conjugates are stable in biological media, have increased permeability through the cell membranes and can be used in gene therapy. 

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The authors declare that there are no conflicts of interest present.