Synthesis and Biophysical Investigations of Oligonucleotides Containing Galactose-Modified DNA, LNA and 2'-Amino-LNA Monomers

Annika Ries, Rajesh Kumar, Chenguang Lou, Tamer Kosbar, Empar Vengut-Climent, Per Trolle Jørgensen, Juan C Morales, Jesper Wengel

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Galactose-modified thymidine, LNA-T and 2'-amino-LNA-T nucleosides were synthesized, converted into the corresponding phosphoramidite derivatives and introduced into short oligonucleotides. Compared to the unmodified control strands, the galactose-modified oligonucleotides in general, and the N2'-functionalized 2'-amino-LNA derivatives in particular, showed improved duplex thermal stability against DNA and RNA complements and increased ability to discriminate mismatches. In addition, especially the 2'-amino-LNA-T derivatives induced remarkable 3'-exonucleolytic stability. These results were further investigated using molecular modelling studies.

Original languageEnglish
JournalThe Journal of Organic Chemistry
Volume81
Issue number22
Pages (from-to)10845-10856
ISSN0022-3263
DOIs
Publication statusPublished - 13. Oct 2016

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Galactose
Oligonucleotides
Monomers
Derivatives
DNA
Molecular modeling
Nucleosides
Thymidine
Thermodynamic stability
RNA
amino-LNA

Cite this

@article{5f58683c5c594b75ae9cf3166162ffba,
title = "Synthesis and Biophysical Investigations of Oligonucleotides Containing Galactose-Modified DNA, LNA and 2'-Amino-LNA Monomers",
abstract = "Galactose-modified thymidine, LNA-T and 2'-amino-LNA-T nucleosides were synthesized, converted into the corresponding phosphoramidite derivatives and introduced into short oligonucleotides. Compared to the unmodified control strands, the galactose-modified oligonucleotides in general, and the N2'-functionalized 2'-amino-LNA derivatives in particular, showed improved duplex thermal stability against DNA and RNA complements and increased ability to discriminate mismatches. In addition, especially the 2'-amino-LNA-T derivatives induced remarkable 3'-exonucleolytic stability. These results were further investigated using molecular modelling studies.",
author = "Annika Ries and Rajesh Kumar and Chenguang Lou and Tamer Kosbar and Empar Vengut-Climent and J{\o}rgensen, {Per Trolle} and Morales, {Juan C} and Jesper Wengel",
year = "2016",
month = "10",
day = "13",
doi = "10.1021/acs.joc.6b01917",
language = "English",
volume = "81",
pages = "10845--10856",
journal = "Journal of Organic Chemistry",
issn = "0022-3263",
publisher = "American Chemical Society",
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}

Synthesis and Biophysical Investigations of Oligonucleotides Containing Galactose-Modified DNA, LNA and 2'-Amino-LNA Monomers. / Ries, Annika; Kumar, Rajesh; Lou, Chenguang; Kosbar, Tamer; Vengut-Climent, Empar; Jørgensen, Per Trolle; Morales, Juan C; Wengel, Jesper.

In: The Journal of Organic Chemistry, Vol. 81, No. 22, 13.10.2016, p. 10845-10856.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Synthesis and Biophysical Investigations of Oligonucleotides Containing Galactose-Modified DNA, LNA and 2'-Amino-LNA Monomers

AU - Ries, Annika

AU - Kumar, Rajesh

AU - Lou, Chenguang

AU - Kosbar, Tamer

AU - Vengut-Climent, Empar

AU - Jørgensen, Per Trolle

AU - Morales, Juan C

AU - Wengel, Jesper

PY - 2016/10/13

Y1 - 2016/10/13

N2 - Galactose-modified thymidine, LNA-T and 2'-amino-LNA-T nucleosides were synthesized, converted into the corresponding phosphoramidite derivatives and introduced into short oligonucleotides. Compared to the unmodified control strands, the galactose-modified oligonucleotides in general, and the N2'-functionalized 2'-amino-LNA derivatives in particular, showed improved duplex thermal stability against DNA and RNA complements and increased ability to discriminate mismatches. In addition, especially the 2'-amino-LNA-T derivatives induced remarkable 3'-exonucleolytic stability. These results were further investigated using molecular modelling studies.

AB - Galactose-modified thymidine, LNA-T and 2'-amino-LNA-T nucleosides were synthesized, converted into the corresponding phosphoramidite derivatives and introduced into short oligonucleotides. Compared to the unmodified control strands, the galactose-modified oligonucleotides in general, and the N2'-functionalized 2'-amino-LNA derivatives in particular, showed improved duplex thermal stability against DNA and RNA complements and increased ability to discriminate mismatches. In addition, especially the 2'-amino-LNA-T derivatives induced remarkable 3'-exonucleolytic stability. These results were further investigated using molecular modelling studies.

U2 - 10.1021/acs.joc.6b01917

DO - 10.1021/acs.joc.6b01917

M3 - Journal article

C2 - 27736097

VL - 81

SP - 10845

EP - 10856

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

SN - 0022-3263

IS - 22

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