In this study, it was found that the arrangement of consecutive thiocarbonyl groups of s(2)T and m(5)s(2)C remarkably stabilized the pre-protonated form of the triplex, and that the stabilization of the pre-protonated form increased the pKa value of a cytosine derivative in the triplex.

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New 3'-terminal deoxyribonucleoside-loading reagents having a silyl-type linker were developed. They were effectively introduced into polymer supports under the conditions of Huisgen [3 + 2] cycloaddition without base protection. Moreover, four unmodified DNA oligomers d[TACCTAAATCCAX] (X = T, A, C, and A) and a base-labile modified DNA 12mer d[A*C*T*C*C*GT*C*T*A*C*G] 16 (A* = 6-N-acetyl-8-aza-7-deaza-2'-deoxyadenosine, C* = 4-N-acetyl-2'-deoxyctydine, T* = 2-thio-T) were successfully synthesized by cleavage of the silyl-type linker using Bu(4)NF under neutral conditions in our N-unprotected phosphoramidite method. In this paper, we also report a new reaction of chlorination of cytosine base using 1,3-dichloro-5,5-dimethylhydantoin.

In the previous study, we developed a method for O-selective phosphorylation, i.e., "the activated phosphite method" for DNA synthesis without base protection. However, the O-selectivity was low in RNA synthesis when the activated phosphite method was used. In this paper, we developed a new method for the O-selective phosphorylation available for the chemical synthesis of aminoacylated RNAs on polymer supports. As the result, it was found that the selectivity of the phosphorylation in RNA synthesis without base protection increased to more than 99% by treatment of the undesired N-P(III) bonds with 1-hydroxyl-6-nitorobenzotriazole, independent of the kind of protecting groups at the 2' position. Moreover, we succeeded in synthesizing a 21 mer oligoRNA without base protection.

In the previous study, we developed a method for O-selective phosphorylation, i.e., "the activated phosphite method" for DNA synthesis without base protection. However, the O-selectivity was low in RNA synthesis when the activated phosphite method was used. In this paper, we developed two new methods for synthesis of RNA oligomers having base-labile functional groups on polymer supports. One is the N-unprotected phosphoramidite method involving P(III)-N bond cleavage. The selectivity of the phosphorylation in RNA synthesis increased to more than 99% by posttreatment of the undesired P(III)-N bonds with 6-nitoro-HOBt and was independent of the kind of protecting groups at the 2' position. Another method is the RNA synthesis involving deprotection of protecting groups of the nucleobases under acidic conditions. It was found that an N,N-dialkylaminomethlene (DAF) group could be easily removed by heat-induced deprotection using HOBt as an acidic promoter.