A Convenient Oligonucleotide Conjugation via Tandem Staudinger Reaction and Amide Bond Formation at the Internucleotidic Phosphate Position

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A Convenient Oligonucleotide Conjugation via Tandem Staudinger Reaction and Amide Bond Formation at the Internucleotidic Phosphate Position. / Klabenkova, Kristina V.; Zhdanova, Polina V.; Burakova, Ekaterina A. et al.

In: International Journal of Molecular Sciences, Vol. 25, No. 4, 2007, 07.02.2024.

Research output: Contribution to journal › Article › peer-review

BibTeX

@article{cabb4c1de68d4827b1f76a9e27b39264,

title = "A Convenient Oligonucleotide Conjugation via Tandem Staudinger Reaction and Amide Bond Formation at the Internucleotidic Phosphate Position",

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.",

keywords = "4-nitrophenyl active esters, antisense oligonucleotide, carboxylic acid group modification, conjugation, nucleic acid, pentafluorobenzyl, pentafluorophenyl, sulfonyl azide, Oligonucleotides/chemistry, Phosphates, Azides, Amides/chemistry, Esters",

author = "Klabenkova, {Kristina V.} and Zhdanova, {Polina V.} and Burakova, {Ekaterina A.} and Bizyaev, {Sergei N.} and Fokina, {Alesya A.} and Stetsenko, {Dmitry A.}",

note = "This work was funded by the Russian Science Foundation (grant No. 22-13-00212) and, in part, by the Ministry of Science and Higher Education of the Russian Federation (project of Novosibirsk State University No. FSUS-2020-0035, oligonucleotide purification and thermal melting analysis).",

year = "2024",

month = feb,

day = "7",

doi = "10.3390/ijms25042007",

language = "English",

volume = "25",

journal = "International Journal of Molecular Sciences",

issn = "1661-6596",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "4",

}

RIS

TY - JOUR

T1 - A Convenient Oligonucleotide Conjugation via Tandem Staudinger Reaction and Amide Bond Formation at the Internucleotidic Phosphate Position

AU - Klabenkova, Kristina V.

AU - Zhdanova, Polina V.

AU - Burakova, Ekaterina A.

AU - Bizyaev, Sergei N.

AU - Fokina, Alesya A.

AU - Stetsenko, Dmitry A.

N1 - This work was funded by the Russian Science Foundation (grant No. 22-13-00212) and, in part, by the Ministry of Science and Higher Education of the Russian Federation (project of Novosibirsk State University No. FSUS-2020-0035, oligonucleotide purification and thermal melting analysis).

PY - 2024/2/7

Y1 - 2024/2/7

N2 - 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.

AB - 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.

KW - 4-nitrophenyl active esters

KW - antisense oligonucleotide

KW - carboxylic acid group modification

KW - conjugation

KW - nucleic acid

KW - pentafluorobenzyl

KW - pentafluorophenyl

KW - sulfonyl azide

KW - Oligonucleotides/chemistry

KW - Phosphates

KW - Azides

KW - Amides/chemistry

KW - Esters

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85185960707&origin=inward&txGid=6a01f4711631a4b0f32e0733980e3288

UR - https://www.mendeley.com/catalogue/d96fdfa3-6f64-322b-8a39-76c8fc511b73/

U2 - 10.3390/ijms25042007

DO - 10.3390/ijms25042007

M3 - Article

C2 - 38396686

VL - 25

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 4

M1 - 2007

ER -

ID: 60224063