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

doi:10.1021/acs.joc.6b01917

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

Department of Physics, Chemistry and Pharmacy

Research output: Contribution to journal › Journal article › Research › peer-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, the 2′-amino-LNA-T derivatives induced remarkable 3′-exonuclease resistance. These results were further investigated using molecular modeling studies.

Original language	English
Journal	The Journal of Organic Chemistry
Volume	81
Issue number	22
Pages (from-to)	10845-10856
ISSN	0022-3263
DOIs	https://doi.org/10.1021/acs.joc.6b01917
Publication status	Published - 13. Oct 2016

Keywords

Biophysical Phenomena
Carbon-13 Magnetic Resonance Spectroscopy
DNA/chemistry
Galactose/chemistry
Models, Molecular
Nucleic Acid Denaturation
Oligonucleotides/chemistry
Proton Magnetic Resonance Spectroscopy
Spectrometry, Mass, Electrospray Ionization
Temperature

Documents & Links

10.1021/acs.joc.6b01917

Cite this

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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, the 2′-amino-LNA-T derivatives induced remarkable 3′-exonuclease resistance. These results were further investigated using molecular modeling studies.",

keywords = "Biophysical Phenomena, Carbon-13 Magnetic Resonance Spectroscopy, DNA/chemistry, Galactose/chemistry, Models, Molecular, Nucleic Acid Denaturation, Oligonucleotides/chemistry, Proton Magnetic Resonance Spectroscopy, Spectrometry, Mass, Electrospray Ionization, Temperature",

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 = oct,

day = "13",

doi = "10.1021/acs.joc.6b01917",

language = "English",

volume = "81",

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journal = "The Journal of Organic Chemistry",

issn = "0022-3263",

publisher = "American Chemical Society",

number = "22",

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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, the 2′-amino-LNA-T derivatives induced remarkable 3′-exonuclease resistance. These results were further investigated using molecular modeling 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, the 2′-amino-LNA-T derivatives induced remarkable 3′-exonuclease resistance. These results were further investigated using molecular modeling studies.

KW - Biophysical Phenomena

KW - Carbon-13 Magnetic Resonance Spectroscopy

KW - DNA/chemistry

KW - Galactose/chemistry

KW - Models, Molecular

KW - Nucleic Acid Denaturation

KW - Oligonucleotides/chemistry

KW - Proton Magnetic Resonance Spectroscopy

KW - Spectrometry, Mass, Electrospray Ionization

KW - Temperature

U2 - 10.1021/acs.joc.6b01917

DO - 10.1021/acs.joc.6b01917

M3 - Journal article

C2 - 27736097

SN - 0022-3263

VL - 81

SP - 10845

EP - 10856

JO - The Journal of Organic Chemistry

JF - The Journal of Organic Chemistry

IS - 22

ER -

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

Abstract

Keywords

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