Oligonucleotide Analogues as Potential Chemotherapeutic Agents

摘要: Oligonucleotides specifically bind to complementary sequences of either genomic DNA or RNA through hydrogen bonding base pairs. In principle, relatively short oligomers (<20 bases) can hybridize with and thus be used for novel drug design strategies involving targeted interference genetic expression at the level transcription translation. Conceivable chemotherapeutic applications predicated on sequence-specific hybridization (“antisense” inhibition) require oligonucleotide analogues that are resistant in vivo degradation by enzymes such as nucleases. Nuclease-resistant having modified internucleoside linkages (e.g., methylphosphonates phosphorothioates) nucleosides 2′-0-methylribose α-anomers) now readily available means automated synthesis, there various classes pendant groups alkylating intercalating agents) attached increase efficacy these analogues. The present account reviews this area research classifying structures mechanisms action, comments stereochemistry. Biological studies briefly summarized, pharmaceutically related topics interest noted.