Synthesis and triplex-forming ability of oligonucleotides bearing 1-substituted 1H-1,2,3-triazole nucleobases.
Using the copper(I)-catalyzed alkyne-azide 1,3-dipolar cycloaddition, a post-elongation modification of 1-ethynyl substituted nucleobases has been employed to construct 18 variations of oligonucleotides from a common oligonucleotide precursor. The triplex-forming ability of each oligonucleotide with dsDNA was evaluated by the UV melting experiment. It was found that triazole nucleobases generally tend to exhibit binding affinities in the following order: CG>TA>AT, GC base pairs. Among the triazole nucleobases examined, a 1-(4-ureidophenyl)triazole provided the best result with regard to affinity and selectivity for the CG base pair.
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. hari@phs.osaka-u.ac.jp
Yoshiyuki
Y
Hari
Motoi
M
Nakahara
Juanjuan
J
Pang
Masaaki
M
Akabane
Takeshi
T
Kuboyama
Satoshi
S
Obika
D001386:Azides / Q000737:chemistry; D020029:Base Pairing; D004247:DNA / Q000737:chemistry*; D015195:Drug Design; D006571:Heterocyclic Compounds; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry*; D010671:Phenylurea Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry
D001386:Azides; D006571:Heterocyclic Compounds; D009841:Oligonucleotides; D010671:Phenylurea Compounds; D014230:Triazoles; C051802:triplex DNA; D004247:DNA