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Backbone modification of nucleic acids: synthesis, structure and therapeutic applications.
Micklefield, Jason
Current Medicinal Chemistry. 2001;8:1157-1179.
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Abstract
A review with 180 refs. Nucleic acids have been extensively modified by replacing the phosphodiester group or the whole sugar-phosphodiester backbone 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 antigen 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 oligodeoxyribonucleotides will be discussed, with a view to their future as novel pharmaceuticals.
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