ボラノホスフェート核酸の効率的な合成法の開発

抄録

Boranophosphate (PB) DNAs and RNAs are promising candidates of oligonucleotide therapeutics because of their attractive features, such as high nuclease resistance and low toxicity. However, the difficulties in synthesizing boranophosphate oligonucleotides hamper the detailed investigation on their physiological and biological properties. Under these circumstances, we have developed efficient synthetic methods of boranophosphate oligonucleotides. Our methodology can be roughly divided into two categories. The first cateogory includes the use of P-boronated nucleotide monomers which facilitate the utilization of general acyl-type amino protecting groups. The second one utilizes oxazaphospholidine monomers those chiral auxiliary can be removed under acidic conditions. Notably, the latter method affords stereo-controlled boranophosphate oligonucleotides with all four nucleobases. Important properties such as a duplex forming ability to the complementary strand, RNase H activity and nuclease resistance are revealed using boranophosphate oligonucleotides synthesized by above mentioned methods.