Zwitterionic oligonucleotides with 2′-O-[3-(N,N-dimethylamino)propyl]-RNA modification: synthesis and properties

A novel 2′-modification, 2′-O-[3-(N,N-dimethylamino)propyl] or 2′-O-DMAP, has been incorporated into oligonucleotides and compared to the known 2′-O-(3-aminopropyl) or 2′-O-AP modification for antisense properties. The 2′-O-DMAP modified oligonucleotides exhibit very high nuclease resistance like the 2′-O-AP modification due to the ‘charge effect’ and maintain high binding affinity to target RNA relative to known modifications when a few 2′-O-DMAP residues are dispersed throughout the oligonucleotide.