High affinity RNA targeting by oligonucleotides displaying aromatic stacking and amino groups in the major groove. Comparison of triazoles and phenylsubstituents

Pawan Kumar, Mick Hornum, Lise Junker Nielsen, Gerald Enderlin, Nicolai Krog Andersen, Christophe Len, Gwénaëlle Hervé, Guillaume Sartori , Poul Nielsen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Three 5-modified 2'-deoxyuridine nucleosides were synthesized and incorporated into oligonucleotides and compared with the previously published 5-(1-phenyl-1,2,3-triazol-4-yl)-2'-deoxyuridine monomer W. The introduction of an aminomethyl group on the phenyl group led to monomer X, which was found to thermally stabilize a 9-mer DNA:RNA duplex, presumably through the partial neutralization of the negative charge of the backbone. By also taking advantage of the stacking interactions in the major groove of two or more of the monomer X, an extremely high thermal stability was obtained. A regioisomer of the phenyltriazole substituent, that is the 5-(4-phenyl-1,2,3-triazol-1-yl)-2'-deoxyuridine monomer Y, was found to destabilize the DNA:RNA duplex significantly, but stacking in the major groove compensated for this when two to four monomers were incorporated consecutively. Finally, the 5-phenyl-2'-deoxyuridine monomer Z was incorporated for comparison, and it was found to give a more neutral influence on duplex stability indicating less efficient stacking interactions. The duplexes were investigated by CD spectroscopy and MD simulations.
OriginalsprogEngelsk
TidsskriftJournal of Organic Chemistry
Vol/bind79
Udgave nummer7
Sider (fra-til)2854-2863
Antal sider10
ISSN0022-3263
DOI
StatusUdgivet - 2014

Citer dette

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title = "High affinity RNA targeting by oligonucleotides displaying aromatic stacking and amino groups in the major groove. Comparison of triazoles and phenylsubstituents",
abstract = "Three 5-modified 2'-deoxyuridine nucleosides were synthesized and incorporated into oligonucleotides and compared with the previously published 5-(1-phenyl-1,2,3-triazol-4-yl)-2'-deoxyuridine monomer W. The introduction of an aminomethyl group on the phenyl group led to monomer X, which was found to thermally stabilize a 9-mer DNA:RNA duplex, presumably through the partial neutralization of the negative charge of the backbone. By also taking advantage of the stacking interactions in the major groove of two or more of the monomer X, an extremely high thermal stability was obtained. A regioisomer of the phenyltriazole substituent, that is the 5-(4-phenyl-1,2,3-triazol-1-yl)-2'-deoxyuridine monomer Y, was found to destabilize the DNA:RNA duplex significantly, but stacking in the major groove compensated for this when two to four monomers were incorporated consecutively. Finally, the 5-phenyl-2'-deoxyuridine monomer Z was incorporated for comparison, and it was found to give a more neutral influence on duplex stability indicating less efficient stacking interactions. The duplexes were investigated by CD spectroscopy and MD simulations.",
author = "Pawan Kumar and Mick Hornum and Nielsen, {Lise Junker} and Gerald Enderlin and Andersen, {Nicolai Krog} and Christophe Len and Gw{\'e}na{\"e}lle Herv{\'e} and Guillaume Sartori and Poul Nielsen",
year = "2014",
doi = "10.1021/jo4025896",
language = "English",
volume = "79",
pages = "2854--2863",
journal = "Journal of Organic Chemistry",
issn = "0022-3263",
publisher = "American Chemical Society",
number = "7",

}

High affinity RNA targeting by oligonucleotides displaying aromatic stacking and amino groups in the major groove. Comparison of triazoles and phenylsubstituents. / Kumar, Pawan; Hornum, Mick; Nielsen, Lise Junker; Enderlin, Gerald; Andersen, Nicolai Krog; Len, Christophe; Hervé, Gwénaëlle; Sartori , Guillaume ; Nielsen, Poul.

I: Journal of Organic Chemistry, Bind 79, Nr. 7, 2014, s. 2854-2863.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - High affinity RNA targeting by oligonucleotides displaying aromatic stacking and amino groups in the major groove. Comparison of triazoles and phenylsubstituents

AU - Kumar, Pawan

AU - Hornum, Mick

AU - Nielsen, Lise Junker

AU - Enderlin, Gerald

AU - Andersen, Nicolai Krog

AU - Len, Christophe

AU - Hervé, Gwénaëlle

AU - Sartori , Guillaume

AU - Nielsen, Poul

PY - 2014

Y1 - 2014

N2 - Three 5-modified 2'-deoxyuridine nucleosides were synthesized and incorporated into oligonucleotides and compared with the previously published 5-(1-phenyl-1,2,3-triazol-4-yl)-2'-deoxyuridine monomer W. The introduction of an aminomethyl group on the phenyl group led to monomer X, which was found to thermally stabilize a 9-mer DNA:RNA duplex, presumably through the partial neutralization of the negative charge of the backbone. By also taking advantage of the stacking interactions in the major groove of two or more of the monomer X, an extremely high thermal stability was obtained. A regioisomer of the phenyltriazole substituent, that is the 5-(4-phenyl-1,2,3-triazol-1-yl)-2'-deoxyuridine monomer Y, was found to destabilize the DNA:RNA duplex significantly, but stacking in the major groove compensated for this when two to four monomers were incorporated consecutively. Finally, the 5-phenyl-2'-deoxyuridine monomer Z was incorporated for comparison, and it was found to give a more neutral influence on duplex stability indicating less efficient stacking interactions. The duplexes were investigated by CD spectroscopy and MD simulations.

AB - Three 5-modified 2'-deoxyuridine nucleosides were synthesized and incorporated into oligonucleotides and compared with the previously published 5-(1-phenyl-1,2,3-triazol-4-yl)-2'-deoxyuridine monomer W. The introduction of an aminomethyl group on the phenyl group led to monomer X, which was found to thermally stabilize a 9-mer DNA:RNA duplex, presumably through the partial neutralization of the negative charge of the backbone. By also taking advantage of the stacking interactions in the major groove of two or more of the monomer X, an extremely high thermal stability was obtained. A regioisomer of the phenyltriazole substituent, that is the 5-(4-phenyl-1,2,3-triazol-1-yl)-2'-deoxyuridine monomer Y, was found to destabilize the DNA:RNA duplex significantly, but stacking in the major groove compensated for this when two to four monomers were incorporated consecutively. Finally, the 5-phenyl-2'-deoxyuridine monomer Z was incorporated for comparison, and it was found to give a more neutral influence on duplex stability indicating less efficient stacking interactions. The duplexes were investigated by CD spectroscopy and MD simulations.

U2 - 10.1021/jo4025896

DO - 10.1021/jo4025896

M3 - Journal article

C2 - 24611639

VL - 79

SP - 2854

EP - 2863

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

SN - 0022-3263

IS - 7

ER -