Sulfonamide bearing oligonucleotides: Simple synthesis and efficient RNA recognition

Four pyrimidine nucleosides wherein a benzensulfonamide group is linked to the C-5 position of the uracil nucleobase through a triazolyl or an alkynyl linker were prepared by Cu(I)-assisted azide-alkyne cycloadditions (CuAAC) or Sonogashira reactions, respectively, and incorporated into oligonucleotides. Efficient pi-pi-stacking between two or more phenyltriazoles in the major groove was found to increase the thermal stability of a DNA: RNA duplex significantly. On the other hand, the alkynyl group was not as efficient in stacking as the triazolyl group. No effect of positional orientation of the sulfonamide group on the stacking efficiency was observed, and the most stable DNA: RNA duplex contained four consecutive sulfonamide substituted phenyltriazole moieties in the major groove. (C) 2012 Elsevier Ltd. All rights reserved.