Novel conformationally constrained 2'-C-methylribonucleosides: synthesis and incorporation into oligonucleotides

Kim Vejlegaard, Christina Wegeberg, Vickie McKee, Jesper Wengel

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Synthesis of two novel conformationally constrained bicyclic ribonucleoside phosphoramidites bearing a 2'-C-methyl substituent has been accomplished. These phosphoramidites were used to incorporate the corresponding 2'-C-methyl nucleotides into oligonucleotides and to study their effects on duplex thermal stability. Whereas the C2'-O4'-linked LNA-type derivative induced severe destabilization of duplexes formed with complementary DNA and RNA, the C3'-O4'-linked derivative induced RNA-selective hybridization with increased affinity relative to that of the unmodified DNA-based probe.

Original languageEnglish
JournalOrganic & Biomolecular Chemistry
Volume16
Issue number8
Pages (from-to)1312-1321
ISSN1477-0520
DOIs
Publication statusPublished - 2018

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Oligonucleotides
Bearings (structural)
Derivatives
Ribonucleosides
Complementary RNA
Thermodynamic stability
Nucleotides
Complementary DNA
RNA
DNA
phosphoramidite

Cite this

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title = "Novel conformationally constrained 2'-C-methylribonucleosides: synthesis and incorporation into oligonucleotides",
abstract = "Synthesis of two novel conformationally constrained bicyclic ribonucleoside phosphoramidites bearing a 2'-C-methyl substituent has been accomplished. These phosphoramidites were used to incorporate the corresponding 2'-C-methyl nucleotides into oligonucleotides and to study their effects on duplex thermal stability. Whereas the C2'-O4'-linked LNA-type derivative induced severe destabilization of duplexes formed with complementary DNA and RNA, the C3'-O4'-linked derivative induced RNA-selective hybridization with increased affinity relative to that of the unmodified DNA-based probe.",
author = "Kim Vejlegaard and Christina Wegeberg and Vickie McKee and Jesper Wengel",
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pages = "1312--1321",
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publisher = "Royal Society of Chemistry",
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Novel conformationally constrained 2'-C-methylribonucleosides : synthesis and incorporation into oligonucleotides. / Vejlegaard, Kim; Wegeberg, Christina; McKee, Vickie; Wengel, Jesper.

In: Organic & Biomolecular Chemistry, Vol. 16, No. 8, 2018, p. 1312-1321 .

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Novel conformationally constrained 2'-C-methylribonucleosides

T2 - synthesis and incorporation into oligonucleotides

AU - Vejlegaard, Kim

AU - Wegeberg, Christina

AU - McKee, Vickie

AU - Wengel, Jesper

PY - 2018

Y1 - 2018

N2 - Synthesis of two novel conformationally constrained bicyclic ribonucleoside phosphoramidites bearing a 2'-C-methyl substituent has been accomplished. These phosphoramidites were used to incorporate the corresponding 2'-C-methyl nucleotides into oligonucleotides and to study their effects on duplex thermal stability. Whereas the C2'-O4'-linked LNA-type derivative induced severe destabilization of duplexes formed with complementary DNA and RNA, the C3'-O4'-linked derivative induced RNA-selective hybridization with increased affinity relative to that of the unmodified DNA-based probe.

AB - Synthesis of two novel conformationally constrained bicyclic ribonucleoside phosphoramidites bearing a 2'-C-methyl substituent has been accomplished. These phosphoramidites were used to incorporate the corresponding 2'-C-methyl nucleotides into oligonucleotides and to study their effects on duplex thermal stability. Whereas the C2'-O4'-linked LNA-type derivative induced severe destabilization of duplexes formed with complementary DNA and RNA, the C3'-O4'-linked derivative induced RNA-selective hybridization with increased affinity relative to that of the unmodified DNA-based probe.

U2 - 10.1039/c7ob02663c

DO - 10.1039/c7ob02663c

M3 - Journal article

C2 - 29392247

VL - 16

SP - 1312

EP - 1321

JO - Organic & Biomolecular Chemistry

JF - Organic & Biomolecular Chemistry

SN - 1477-0520

IS - 8

ER -