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- Title
A Convenient Oligonucleotide Conjugation via Tandem Staudinger Reaction and Amide Bond Formation at the Internucleotidic Phosphate Position.
- Authors
Klabenkova, Kristina V.; Zhdanova, Polina V.; Burakova, Ekaterina A.; Bizyaev, Sergei N.; Fokina, Alesya A.; Stetsenko, Dmitry A.
- Abstract
Staudinger reaction on the solid phase between an electronodeficit organic azide, such as sulfonyl azide, and the phosphite triester formed upon phosphoramidite coupling is a convenient method for the chemical modification of oligonucleotides at the internucleotidic phosphate position. In this work, 4-carboxybenzenesulfonyl azide, either with a free carboxy group or in the form of an activated ester such as pentafluorophenyl, 4-nitrophenyl, or pentafluorobenzyl, was used to introduce a carboxylic acid function to the terminal or internal internucleotidic phosphate of an oligonucleotide via the Staudinger reaction. A subsequent treatment with excess primary alkyl amine followed by the usual work-up, after prior activation with a suitable peptide coupling agent such as a uronium salt/1-hydroxybenzotriazole in the case of a free carboxyl, afforded amide-linked oligonucleotide conjugates in good yields including multiple conjugations of up to the exhaustive modification at each phosphate position for a weakly activated pentafluorobenzyl ester, whereas more strongly activated and, thus, more reactive aryl esters provided only single conjugations at the 5′-end. The conjugates synthesized include those with di- and polyamines that introduce a positively charged side chain to potentially assist the intracellular delivery of the oligonucleotide.
- Subjects
ARYL esters; AMIDES; PHOSPHATES; FREE groups; CARBOXYLIC acids; PEPTIDES; PHORBOL esters
- Publication
International Journal of Molecular Sciences, 2024, Vol 25, Issue 4, p2007
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms25042007