title: Benzylidene acetal type bridged nucleic acids: changes in properties upon cleavage of the bridge triggered by external stimuli.
abstract: 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Morihiro
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kodama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Obika
mesh_terms: D000080:Acetals / Q000737:chemistry*; D001597:Benzylidene Compounds / Q000737:chemistry*; D008027:Light; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009696:Nucleic Acids / Q000737:chemistry*; D009841:Oligonucleotides / Q000737:chemistry*
chemical_list: D000080:Acetals; D001597:Benzylidene Compounds; D009696:Nucleic Acids; D009841:Oligonucleotides