Resumé
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Journal of Organic Chemistry |
| Vol/bind | 79 |
| Udgave nummer | 7 |
| Sider (fra-til) | 2854-2863 |
| Antal sider | 10 |
| ISSN | 0022-3263 |
| DOI | |
| Status | Udgivet - 2014 |
Citer dette
}
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 tidsskrift › Tidsskriftartikel › Forskning › peer 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 -