Synthesis and structural studies of S-type/N-type-locked/frozen nucleoside analogues and their incorporation in RNA-selective, nuclease resistant 2′–5′ linked oligonucleotides

2′-endo locked or frozen (S-type)/3′-endo locked or frozen (N-type) nucleoside analogues were synthesized. Conformational analysis based on ³J_HH and NOE measurements is presented which is further confirmed by X-ray crystal structural studies. 2′–5′ isoDNA oligonucleotides (ON) were synthesized using these modified nucleoside analogues and UV-T_m studies of the resultant 2′–5′ isoDNA : RNA duplexes reflect the site- and sequence-dependent effects and confirm that the S-type sugar conformations were preferred over the N-type sugar geometry in such duplexes.