Syntheses and properties of novel conformationally restrained nucleoside analogues

Abstract

This account describes our syntheses and conformational analyses of the bicyclic nucleoside analogues, 3′-O,4′-C-methyleneribonucleosides (4-BC), 3′-amino-3′-deoxy-3′-O,4′-C-methyleneribonucleosides (aza 4-BC), 2′-O,4′-C-methyleneribonucleosides (5-BC), and 3′-amino- and 3′-azido-3′deoxy-2′-O,4′-C-methyleneribonucleosides (aza 5-BC). The nucleoside analogues (4-BC and 5-BC) were effectively introduced into oligonucleotides by using a DNA synthesizer. Furthermore, unprecedented hybridizing ability towards complementary RNA and DNA, potent triplex-forming ability, and sufficient enzymatic stability of these modified oligonucleotides were also confirmed. From these studies, we believe that these conformationally restrained nucleoside analogues are good candidates for practical antisense/antigene molecules.