title: Duplex and triplex formation of mixed pyrimidine oligonucleotides with stacking of phenyl-triazole moieties in the major groove.
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.
authors.affiliation: Nucleic Acid Center, Department of Physics and Chemistry, University of Southern Denmark, 5230 Odense M, Denmark.
authors.forename: Nicolai Krog
authors.initials: NK
authors.lastname: Andersen
authors.forename: Holger
authors.initials: H
authors.lastname: Døssing
authors.forename: Frank
authors.initials: F
authors.lastname: Jensen
authors.forename: Birte
authors.initials: B
authors.lastname: Vester
authors.forename: Poul
authors.initials: P
authors.lastname: Nielsen
mesh_terms: D001483:Base Sequence; D002942:Circular Dichroism; D018076:DNA, Complementary / Q000737:chemistry*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009705:Nucleosides / Q000737:chemistry*; D009711:Nucleotides / Q000737:chemistry*; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry*; D011743:Pyrimidines / Q000737:chemistry*; D018075:RNA, Complementary / Q000737:chemistry*; D014230:Triazoles / Q000737:chemistry*
chemical_list: C569117:5-(1-phenyl-1,2,3-triazol-4-yl)-2'-deoxycytidine; C569118:5-(1-phenyl-1,2,3-triazol-4-yl)-2'-deoxyuridine; D018076:DNA, Complementary; D009705:Nucleosides; D009711:Nucleotides; D009841:Oligonucleotides; D011743:Pyrimidines; D018075:RNA, Complementary; D014230:Triazoles; D003841:Deoxycytidine; C030986:pyrimidine; D003857:Deoxyuridine