Backbone modification of nucleic acids: synthesis, structure and therapeutic applications.
Nucleic acids have been extensively modified by replacing the phosphodiester group or the whole sugar phosphodiester with alternative anionic, neutral and cationic structures. Several of these modified oligonucleotides exhibit improved properties including enhanced recognition and binding to RNA, duplex DNA and proteins. This has resulted in the development of new and more potent antisense and antigene agents, as well as aptamers. Furthermore, backbone modified oligonucleotides have also been used in the development of several alternative strategies, which rely on altogether different mechanisms of action and show significant promise for therapeutic intervention. In this review the latest advances in the synthesis and evaluation of the most promising backbone modified oligos will be discussed, with a view to their future as novel pharmaceuticals.
Micklefield
J
J
Department of Chemistry, University of Manchester Institute of Science and Technology, Faraday Building, Sackville Street, P.O Box 88, Manchester, M60 1QD, UK.
D000577:Amides / Q000737:chemistry*; D001880:Boranes / Q000737:chemistry; D015195:Drug Design; D009690:Nucleic Acid Conformation; D009696:Nucleic Acids / Q000737:chemistry* / Q000627:therapeutic use; D009943:Organophosphorus Compounds / Q000737:chemistry*; D020135:Peptide Nucleic Acids / Q000737:chemistry*; D010756:Phosphoric Acids / Q000737:chemistry*; D011355:Prodrugs / Q000737:chemistry* / Q000627:therapeutic use
D000577:Amides; D001880:Boranes; D009696:Nucleic Acids; D009943:Organophosphorus Compounds; D020135:Peptide Nucleic Acids; D010756:Phosphoric Acids; D011355:Prodrugs; C032627:methylphosphonic acid; C011067:phosphoramidic acid