Duplex and Triplex Formation of Mixed Pyrimidine Oligonucleotides with Stacking of Phenyl-triazole Moieties in the Major Groove

Nicolai Krog Andersen, Holger Døssing, Frank Jensen, Birte Vester, Poul Nielsen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

5-(1-Phenyl-1,2,3-triazol-4-yl)-2'-deoxycytidine was synthesized from a modified CuAAC protocol and incorporated into mixed pyrimidine oligonucleotide sequences together with the corresponding 5-(1-phenyl-1,2,3-triazol-4-yl)-2'-deoxyuridine. With consecutive incorporations of the two modified nucleosides, improved duplex formation with a complementary RNA and improved triplex formation with a complementary DNA duplex were observed. The improvement is due to π-π stacking of the phenyl-triazole moieties in the major groove. The strongest stacking and most pronounced positive influence on thermal stability was found in between the uridine analogues or with the cytidine analogue placed in the 3' direction to the uridine analogue. Modeling indicated a different orientation of the phenyl-triazole moieties in the major groove to account for the difference between the two nucleotides. The modified oligonucleotides were all found to be significantly stabilized toward nucleolytic degration.
OriginalsprogEngelsk
TidsskriftJournal of Organic Chemistry
Vol/bind76
Udgave nummer15
Sider (fra-til)6177-87
Antal sider11
ISSN0022-3263
DOI
StatusUdgivet - 5. aug. 2011

Fingeraftryk

Triazoles
Uridine
Oligonucleotides
Cytidine
Complementary RNA
Nucleosides
Thermodynamic stability
Nucleotides
Complementary DNA
pyrimidine
Direction compound
5-(1-phenyl-1,2,3-triazol-4-yl)-2'-deoxyuridine
5-(1-phenyl-1,2,3-triazol-4-yl)-2'-deoxycytidine

Citer dette

Andersen, Nicolai Krog ; Døssing, Holger ; Jensen, Frank ; Vester, Birte ; Nielsen, Poul. / Duplex and Triplex Formation of Mixed Pyrimidine Oligonucleotides with Stacking of Phenyl-triazole Moieties in the Major Groove. I: Journal of Organic Chemistry. 2011 ; Bind 76, Nr. 15. s. 6177-87.
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abstract = "5-(1-Phenyl-1,2,3-triazol-4-yl)-2'-deoxycytidine was synthesized from a modified CuAAC protocol and incorporated into mixed pyrimidine oligonucleotide sequences together with the corresponding 5-(1-phenyl-1,2,3-triazol-4-yl)-2'-deoxyuridine. With consecutive incorporations of the two modified nucleosides, improved duplex formation with a complementary RNA and improved triplex formation with a complementary DNA duplex were observed. The improvement is due to π-π stacking of the phenyl-triazole moieties in the major groove. The strongest stacking and most pronounced positive influence on thermal stability was found in between the uridine analogues or with the cytidine analogue placed in the 3' direction to the uridine analogue. Modeling indicated a different orientation of the phenyl-triazole moieties in the major groove to account for the difference between the two nucleotides. The modified oligonucleotides were all found to be significantly stabilized toward nucleolytic degration.",
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Duplex and Triplex Formation of Mixed Pyrimidine Oligonucleotides with Stacking of Phenyl-triazole Moieties in the Major Groove. / Andersen, Nicolai Krog; Døssing, Holger; Jensen, Frank; Vester, Birte; Nielsen, Poul.

I: Journal of Organic Chemistry, Bind 76, Nr. 15, 05.08.2011, s. 6177-87.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Duplex and Triplex Formation of Mixed Pyrimidine Oligonucleotides with Stacking of Phenyl-triazole Moieties in the Major Groove

AU - Andersen, Nicolai Krog

AU - Døssing, Holger

AU - Jensen, Frank

AU - Vester, Birte

AU - Nielsen, Poul

PY - 2011/8/5

Y1 - 2011/8/5

N2 - 5-(1-Phenyl-1,2,3-triazol-4-yl)-2'-deoxycytidine was synthesized from a modified CuAAC protocol and incorporated into mixed pyrimidine oligonucleotide sequences together with the corresponding 5-(1-phenyl-1,2,3-triazol-4-yl)-2'-deoxyuridine. With consecutive incorporations of the two modified nucleosides, improved duplex formation with a complementary RNA and improved triplex formation with a complementary DNA duplex were observed. The improvement is due to π-π stacking of the phenyl-triazole moieties in the major groove. The strongest stacking and most pronounced positive influence on thermal stability was found in between the uridine analogues or with the cytidine analogue placed in the 3' direction to the uridine analogue. Modeling indicated a different orientation of the phenyl-triazole moieties in the major groove to account for the difference between the two nucleotides. The modified oligonucleotides were all found to be significantly stabilized toward nucleolytic degration.

AB - 5-(1-Phenyl-1,2,3-triazol-4-yl)-2'-deoxycytidine was synthesized from a modified CuAAC protocol and incorporated into mixed pyrimidine oligonucleotide sequences together with the corresponding 5-(1-phenyl-1,2,3-triazol-4-yl)-2'-deoxyuridine. With consecutive incorporations of the two modified nucleosides, improved duplex formation with a complementary RNA and improved triplex formation with a complementary DNA duplex were observed. The improvement is due to π-π stacking of the phenyl-triazole moieties in the major groove. The strongest stacking and most pronounced positive influence on thermal stability was found in between the uridine analogues or with the cytidine analogue placed in the 3' direction to the uridine analogue. Modeling indicated a different orientation of the phenyl-triazole moieties in the major groove to account for the difference between the two nucleotides. The modified oligonucleotides were all found to be significantly stabilized toward nucleolytic degration.

U2 - 10.1021/jo200919y

DO - 10.1021/jo200919y

M3 - Journal article

VL - 76

SP - 6177

EP - 6187

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

SN - 0022-3263

IS - 15

ER -