Synthesis and triplex-forming ability of oligonucleotides bearing 1-substituted 1H-1,2,3-triazole nucleobases

• Published in: Bioorganic & medicinal chemistry Vol. 19; no. 3; pp. 1162 - 1166
• Main Authors: Hari, Yoshiyuki, Nakahara, Motoi, Pang, Juanjuan, Akabane, Masaaki, Kuboyama, Takeshi, Obika, Satoshi
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.02.2011; Elsevier
• Subjects: Azides - chemistry; Base Pairing; Base pairs; Biological and medical sciences; copper; DNA - chemistry; Drug Design; Fundamental and applied biological sciences. Psychology; Heterocyclic Compounds; Intermolecular phenomena; melting; Miscellaneous; Molecular biophysics; oligonucleotides; Oligonucleotides - chemical synthesis; Oligonucleotides - chemistry; Phenylurea Compounds - chemical synthesis; Phenylurea Compounds - chemistry; triazoles; Triazoles - chemical synthesis; Triazoles - chemistry; Purine derivatives; Acetylenic compound; Molecular structure; Organic azide; Organic phosphoramidite; Secondary structure; CG recognition; Double stranded DNA; Synthesis; GC rich sequence; Triple helix; Triple helical structure; Benzenic compound; Pyrimidine derivatives; Ureas; Oligonucleotide; Click chemistry; Chemical synthesis; Recognition
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2010.12.049

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.