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Convenient Solid-Phase Attachment of Small-Molecule Ligands to Oligonucleotides via a Biodegradable Acid-Labile P-N-Bond. / Kropacheva, Nadezhda O; Golyshkin, Arseniy A; Vorobyeva, Mariya A et al.

In: Molecules (Basel, Switzerland), Vol. 28, No. 4, 1904, 16.02.2023.

Research output: Contribution to journalArticlepeer-review

Harvard

Kropacheva, NO, Golyshkin, AA, Vorobyeva, MA & Meschaninova, MI 2023, 'Convenient Solid-Phase Attachment of Small-Molecule Ligands to Oligonucleotides via a Biodegradable Acid-Labile P-N-Bond', Molecules (Basel, Switzerland), vol. 28, no. 4, 1904. https://doi.org/10.3390/molecules28041904

APA

Kropacheva, N. O., Golyshkin, A. A., Vorobyeva, M. A., & Meschaninova, M. I. (2023). Convenient Solid-Phase Attachment of Small-Molecule Ligands to Oligonucleotides via a Biodegradable Acid-Labile P-N-Bond. Molecules (Basel, Switzerland), 28(4), [1904]. https://doi.org/10.3390/molecules28041904

Vancouver

Kropacheva NO, Golyshkin AA, Vorobyeva MA, Meschaninova MI. Convenient Solid-Phase Attachment of Small-Molecule Ligands to Oligonucleotides via a Biodegradable Acid-Labile P-N-Bond. Molecules (Basel, Switzerland). 2023 Feb 16;28(4):1904. doi: 10.3390/molecules28041904

Author

Kropacheva, Nadezhda O ; Golyshkin, Arseniy A ; Vorobyeva, Mariya A et al. / Convenient Solid-Phase Attachment of Small-Molecule Ligands to Oligonucleotides via a Biodegradable Acid-Labile P-N-Bond. In: Molecules (Basel, Switzerland). 2023 ; Vol. 28, No. 4.

BibTeX

@article{80d0af958b644fa58dcaea7253101918,
title = "Convenient Solid-Phase Attachment of Small-Molecule Ligands to Oligonucleotides via a Biodegradable Acid-Labile P-N-Bond",
abstract = "One of the key problems in the design of therapeutic and diagnostic oligonucleotides is the attachment of small-molecule ligands for targeted deliveries in such a manner that provides the controlled release of the oligonucleotide at a certain moment. Here, we propose a novel, convenient approach for attaching ligands to the 5'-end of the oligonucleotide via biodegradable, acid-labile phosphoramide linkage. The method includes the activation of the 5'-terminal phosphate of the fully protected, support-bound oligonucleotide, followed by interaction with a ligand bearing the primary amino group. This technique is simple to perform, allows for forcing the reaction to completion by adding excess soluble reactant, eliminates the problem of the limited solubility of reagents, and affords the possibility of using different solvents, including water/organic media. We demonstrated the advantages of this approach by synthesizing and characterizing a wide variety of oligonucleotide 5'-conjugates with different ligands, such as cholesterol, aliphatic oleylamine, and p-anisic acid. The developed method suits different types of oligonucleotides (deoxyribo-, 2'-O-methylribo-, ribo-, and others).",
keywords = "5′-functionalization, conjugates of oligonucleotides, pH-sensitive phosphoramidate linkage, siRNA, small molecules, solid-phase synthesis",
author = "Kropacheva, {Nadezhda O} and Golyshkin, {Arseniy A} and Vorobyeva, {Mariya A} and Meschaninova, {Mariya I}",
note = "Funding: This research was funded by Russian Scientific Foundation: 19-14-00251.",
year = "2023",
month = feb,
day = "16",
doi = "10.3390/molecules28041904",
language = "English",
volume = "28",
journal = "Molecules",
issn = "1420-3049",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "4",

}

RIS

TY - JOUR

T1 - Convenient Solid-Phase Attachment of Small-Molecule Ligands to Oligonucleotides via a Biodegradable Acid-Labile P-N-Bond

AU - Kropacheva, Nadezhda O

AU - Golyshkin, Arseniy A

AU - Vorobyeva, Mariya A

AU - Meschaninova, Mariya I

N1 - Funding: This research was funded by Russian Scientific Foundation: 19-14-00251.

PY - 2023/2/16

Y1 - 2023/2/16

N2 - One of the key problems in the design of therapeutic and diagnostic oligonucleotides is the attachment of small-molecule ligands for targeted deliveries in such a manner that provides the controlled release of the oligonucleotide at a certain moment. Here, we propose a novel, convenient approach for attaching ligands to the 5'-end of the oligonucleotide via biodegradable, acid-labile phosphoramide linkage. The method includes the activation of the 5'-terminal phosphate of the fully protected, support-bound oligonucleotide, followed by interaction with a ligand bearing the primary amino group. This technique is simple to perform, allows for forcing the reaction to completion by adding excess soluble reactant, eliminates the problem of the limited solubility of reagents, and affords the possibility of using different solvents, including water/organic media. We demonstrated the advantages of this approach by synthesizing and characterizing a wide variety of oligonucleotide 5'-conjugates with different ligands, such as cholesterol, aliphatic oleylamine, and p-anisic acid. The developed method suits different types of oligonucleotides (deoxyribo-, 2'-O-methylribo-, ribo-, and others).

AB - One of the key problems in the design of therapeutic and diagnostic oligonucleotides is the attachment of small-molecule ligands for targeted deliveries in such a manner that provides the controlled release of the oligonucleotide at a certain moment. Here, we propose a novel, convenient approach for attaching ligands to the 5'-end of the oligonucleotide via biodegradable, acid-labile phosphoramide linkage. The method includes the activation of the 5'-terminal phosphate of the fully protected, support-bound oligonucleotide, followed by interaction with a ligand bearing the primary amino group. This technique is simple to perform, allows for forcing the reaction to completion by adding excess soluble reactant, eliminates the problem of the limited solubility of reagents, and affords the possibility of using different solvents, including water/organic media. We demonstrated the advantages of this approach by synthesizing and characterizing a wide variety of oligonucleotide 5'-conjugates with different ligands, such as cholesterol, aliphatic oleylamine, and p-anisic acid. The developed method suits different types of oligonucleotides (deoxyribo-, 2'-O-methylribo-, ribo-, and others).

KW - 5′-functionalization

KW - conjugates of oligonucleotides

KW - pH-sensitive phosphoramidate linkage

KW - siRNA

KW - small molecules

KW - solid-phase synthesis

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85149054301&origin=inward&txGid=ce3f3c4828c866512a020ef7df71af80

UR - https://www.mendeley.com/catalogue/f7a542c6-c7cb-397d-ac69-628185df47e5/

U2 - 10.3390/molecules28041904

DO - 10.3390/molecules28041904

M3 - Article

C2 - 36838892

VL - 28

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 4

M1 - 1904

ER -

ID: 44521550