Development of Triplex Forming Oligonucleotide Including Artificial Nucleoside Analogues for the Antigene Strategy
The sequence-specific triplex formation against duplex DNA offers a potential basis for genome targeting technology, such as diagnostics, regulation of gene expression and sequencing technologies. In an antiparallel triplex DNA, a purine-rich triplex forming oligonucleotide (TFO) consisting of a dG, dA or T forms two reverse Hoogsteen hydrogen bonds with a GC, AT or AT base pair of the duplex DNA, respectively, with a high selectivity in a sequence specific manner. However, there is no natural nucleoside which can recognize the inverted CG and TA base pair of the duplex DNA. Therefore, the development of recognition molecules for the CG and TA inversion sites with a high stability and selectivity has been demanded for the triplex forming technology. In this chapter, we describe the design and synthesis of W-shaped nucleoside analogues (WNA-βT) and pseudo-dC derivatives (MeAP-ΨdC) for selective recognition of the TA and CG base pair, respectively, to expand the triplex-forming sequence.
KeywordsAntiparallel triplex DNA Antigene Inhibition of gene expression Anti-proliferative effect Artificial nucleoside analogues Inversion site
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