A bridged nucleic acid, 2',4'-BNA super(COC): synthesis of fully modified oligonucleotides bearing thymine, 5-methylcytosine, adenine and guanine 2',4'-BNA super(COC) monomers and RNA-selective nucleic-acid recognition

Recently, we synthesized pyrimidine derivatives of the 2'-O,4'-C-methyle noxymethylene-bridged nucleic-acid (2',4'-BNA super(COC)) monomer, the sugar conformation of which is restricted in N-type conformation by a seven-membered bridged structure. Oligonucleotides (BNA super(COC)) containing this monomer show high affinity with complementary single-stranded RNA and significant resistance to nuclease degradation. Here, BNA super(COC) consisting of 2',4'-BNA super(COC) monomers bearing all four bases, namely thymine, 5-methylcytosine, adenine and guanine was efficiently synthesized and properties of duplexes containing the 2',4'-BNA super(COC) monomers were investigated by UV melting experiments and circular dichroism (CD) spectroscopy. The UV melting curve analyses showed that the BNA super(COC)/BNA super(COC) duplex possessed excellent thermal stability and that the BNA super(COC) increased thermal stability with a complementary RNA strand. On the other hand, BNA super(COC)/DNA heteroduplexes showed almost the same thermal stability as RNA/DNA heteroduplexes. Furthermore, mismatched sequence studies showed that BNA super(COC) generally improved the sequence selectivity with Watson-Crick base-pairing compared to the corresponding natural DNA and RNA. A CD spectroscopic analysis indicated that the BNA super(COC) formed duplexes with complementary DNA and RNA in a manner similar to natural RNA.