SYNTHESIS OF CONJUGATES OF OLIGONUCLEOTIDES AND 11,11-D2-LINOLEIC ACID DERIVATIVES VIA AZIDE-ALKYNE CYCLOADDITION

M. A. Fomich; A. V. Bekish; O. L. Sharko; K. N. Prokhorevich; V. V. Shmanai

doi:10.29235/1561-8331-2018-54-1-46-57

SYNTHESIS OF CONJUGATES OF OLIGONUCLEOTIDES AND 11,11-D2-LINOLEIC ACID DERIVATIVES VIA AZIDE-ALKYNE CYCLOADDITION

M. A. Fomich, A. V. Bekish, O. L. Sharko, K. N. Prokhorevich, V. V. Shmanai

https://doi.org/10.29235/1561-8331-2018-54-1-46-57

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Abstract

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.

Keywords

polyunsaturated fatty acids, oligonucleotides, bioconjugates, click chemistry

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ISSN 1561-8331 (Print)
ISSN 2524-2342 (Online)

Proceedings of the National Academy of Sciences of Belarus, Chemical Series

SYNTHESIS OF CONJUGATES OF OLIGONUCLEOTIDES AND 11,11-D2-LINOLEIC ACID DERIVATIVES VIA AZIDE-ALKYNE CYCLOADDITION

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Proceedings of the National Academy of Sciences of Belarus, Chemical Series

SYNTHESIS OF CONJUGATES OF OLIGONUCLEOTIDES AND 11,11-D2-LINOLEIC ACID DERIVATIVES VIA AZIDE-ALKYNE CYCLOADDITION

Full Text:

Abstract

Keywords

About the Authors

References

Review

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