Benzylidene acetal type bridged nucleic acids: changes in properties upon cleavage of the bridge triggered by external stimuli.

Four classes of benzylidene acetal type bridged nucleic acids (BA-BNAs) were designed with 2',4'-bridged structures that cleaved upon exposure to appropriate external stimuli. Cleavage of 6-nitroveratrylidene and 2-nitrobenzylidene acetal type BNA bridges occurred upon photoirradiation and subsequent treatment with thiol caused changes in secondary structure to afford 4'-C-hydroxymethyl RNA. Benzylidene and 4-nitrobenzylidene acetal type BNA responded to acids and reducing agents, respectively, resulting in hydrolysis of the acetal-bridged structure. Cleavage of the bridge removed sugar conformational restrictions and changed the duplex- and triplex-forming properties of the BNA-modified oligonucleotides. Moreover, oligonucleotides incorporating a single BA-BNA modification had considerably improved stability toward 3'-exonuclease, which was lost upon cleavage of the bridge. Thus, these new BNAs may be useful as therapeutic and detection tools by sensing various environments.