Synthesis and thermal denaturation studies of novel 2'-O,3'-C-linked bicyclic oligonucleotides with a methoxy or a piperazino group facing the major groove of nucleic acid duplexes

Michael Raunkjær, M.D: Sørensen, Jesper Wengel

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

With the aim of evaluating duplex stabilities of oligonucleotides (ONs) with major groove facing functionalities, two novel 2′-O,3′-C-linked bicyclic nucleoside phosphoramidite building blocks were synthesized by routes involving regioselective O-methylation or piperazine attachment using carbonyldiimidazole coupling chemistry. The novel monomers were incorporated into 9-mer mixed base ONs and the thermal stability toward complementary single stranded DNA and RNA was evaluated by thermal denaturation experiments. O-methylated ONs confirmed the applicability of the functionalized bicylic sugar unit for attachment of groups facing the major groove and satisfactory binding properties towards the RNA complement were observed. For the piperazino modified ONs, experiments were performed in aqueous buffers with low (40 mM) and medium (110 mM) salt concentrations, at pH 5 and pH 7. A change from a medium to a low salt concentration induced a significant relative increase in the thermal stability of modified duplexes toward both DNA and RNA complements, which suggests protonation of the piperazino group under the experimental conditions applied.

OriginalsprogEngelsk
TidsskriftOrganic & Biomolecular Chemistry
Vol/bind2005
Udgave nummer1
Sider (fra-til)130-135
ISSN1477-0520
DOI
StatusUdgivet - 2005

Fingeraftryk

Denaturation
Oligonucleotides
Nucleic Acids
RNA
Thermodynamic stability
Salts
Methylation
Single-Stranded DNA
Protonation
Nucleosides
Sugars
Buffers
Monomers
Experiments
Hot Temperature
DNA

Citer dette

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title = "Synthesis and thermal denaturation studies of novel 2'-O,3'-C-linked bicyclic oligonucleotides with a methoxy or a piperazino group facing the major groove of nucleic acid duplexes",
abstract = "With the aim of evaluating duplex stabilities of oligonucleotides (ONs) with major groove facing functionalities, two novel 2′-O,3′-C-linked bicyclic nucleoside phosphoramidite building blocks were synthesized by routes involving regioselective O-methylation or piperazine attachment using carbonyldiimidazole coupling chemistry. The novel monomers were incorporated into 9-mer mixed base ONs and the thermal stability toward complementary single stranded DNA and RNA was evaluated by thermal denaturation experiments. O-methylated ONs confirmed the applicability of the functionalized bicylic sugar unit for attachment of groups facing the major groove and satisfactory binding properties towards the RNA complement were observed. For the piperazino modified ONs, experiments were performed in aqueous buffers with low (40 mM) and medium (110 mM) salt concentrations, at pH 5 and pH 7. A change from a medium to a low salt concentration induced a significant relative increase in the thermal stability of modified duplexes toward both DNA and RNA complements, which suggests protonation of the piperazino group under the experimental conditions applied.",
author = "Michael Raunkj{\ae}r and M.D: S{\o}rensen and Jesper Wengel",
year = "2005",
doi = "10.1039/B414454F",
language = "English",
volume = "2005",
pages = "130--135",
journal = "Organic & Biomolecular Chemistry",
issn = "1477-0520",
publisher = "Royal Society of Chemistry",
number = "1",

}

Synthesis and thermal denaturation studies of novel 2'-O,3'-C-linked bicyclic oligonucleotides with a methoxy or a piperazino group facing the major groove of nucleic acid duplexes. / Raunkjær, Michael; Sørensen, M.D:; Wengel, Jesper.

I: Organic & Biomolecular Chemistry, Bind 2005, Nr. 1, 2005, s. 130-135.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Synthesis and thermal denaturation studies of novel 2'-O,3'-C-linked bicyclic oligonucleotides with a methoxy or a piperazino group facing the major groove of nucleic acid duplexes

AU - Raunkjær, Michael

AU - Sørensen, M.D:

AU - Wengel, Jesper

PY - 2005

Y1 - 2005

N2 - With the aim of evaluating duplex stabilities of oligonucleotides (ONs) with major groove facing functionalities, two novel 2′-O,3′-C-linked bicyclic nucleoside phosphoramidite building blocks were synthesized by routes involving regioselective O-methylation or piperazine attachment using carbonyldiimidazole coupling chemistry. The novel monomers were incorporated into 9-mer mixed base ONs and the thermal stability toward complementary single stranded DNA and RNA was evaluated by thermal denaturation experiments. O-methylated ONs confirmed the applicability of the functionalized bicylic sugar unit for attachment of groups facing the major groove and satisfactory binding properties towards the RNA complement were observed. For the piperazino modified ONs, experiments were performed in aqueous buffers with low (40 mM) and medium (110 mM) salt concentrations, at pH 5 and pH 7. A change from a medium to a low salt concentration induced a significant relative increase in the thermal stability of modified duplexes toward both DNA and RNA complements, which suggests protonation of the piperazino group under the experimental conditions applied.

AB - With the aim of evaluating duplex stabilities of oligonucleotides (ONs) with major groove facing functionalities, two novel 2′-O,3′-C-linked bicyclic nucleoside phosphoramidite building blocks were synthesized by routes involving regioselective O-methylation or piperazine attachment using carbonyldiimidazole coupling chemistry. The novel monomers were incorporated into 9-mer mixed base ONs and the thermal stability toward complementary single stranded DNA and RNA was evaluated by thermal denaturation experiments. O-methylated ONs confirmed the applicability of the functionalized bicylic sugar unit for attachment of groups facing the major groove and satisfactory binding properties towards the RNA complement were observed. For the piperazino modified ONs, experiments were performed in aqueous buffers with low (40 mM) and medium (110 mM) salt concentrations, at pH 5 and pH 7. A change from a medium to a low salt concentration induced a significant relative increase in the thermal stability of modified duplexes toward both DNA and RNA complements, which suggests protonation of the piperazino group under the experimental conditions applied.

U2 - 10.1039/B414454F

DO - 10.1039/B414454F

M3 - Journal article

VL - 2005

SP - 130

EP - 135

JO - Organic & Biomolecular Chemistry

JF - Organic & Biomolecular Chemistry

SN - 1477-0520

IS - 1

ER -