A bridged nucleic acid, 2',4'-BNA COC: synthesis of fully modified oligonucleotides bearing thymine, 5-methylcytosine, adenine and guanine 2',4'-BNA COC monomers and RNA-selective nucleic-acid recognition.
Recently, we synthesized pyrimidine derivatives of the 2'-O,4'-C-methylenoxymethylene-bridged nucleic-acid (2',4'-BNA(COC)) monomer, the sugar conformation of which is restricted in N-type conformation by a seven-membered bridged structure. Oligonucleotides (BNA(COC)) containing this monomer show high affinity with complementary single-stranded RNA and significant resistance to nuclease degradation. Here, BNA(COC) consisting of 2',4'-BNA(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(COC) monomers were investigated by UV melting experiments and circular dichroism (CD) spectroscopy. The UV melting curve analyses showed that the BNA(COC)/BNA(COC) duplex possessed excellent thermal stability and that the BNA(COC) increased thermal stability with a complementary RNA strand. On the other hand, BNA(COC)/DNA heteroduplexes showed almost the same thermal stability as RNA/DNA heteroduplexes. Furthermore, mismatched sequence studies showed that BNA(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(COC) formed duplexes with complementary DNA and RNA in a manner similar to natural RNA.
Mitsuoka
Yasunori
Y
Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.
Kodama
Tetsuya
T
Ohnishi
Ryo
R
Hari
Yoshiyuki
Y
Imanishi
Takeshi
T
Obika
Satoshi
S
D044503:5-Methylcytosine / Q000737:chemistry; D000225:Adenine / Q000737:chemistry; D020137:Base Pair Mismatch; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis / Q000737:chemistry; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry; D006147:Guanine / Q000737:chemistry; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009696:Nucleic Acids / Q000737:chemistry*; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry*; D012313:RNA / Q000737:chemistry*; D013941:Thymine / Q000737:chemistry
D001952:Bridged-Ring Compounds; D009696:Nucleic Acids; D009841:Oligonucleotides; D006147:Guanine; D012313:RNA; D044503:5-Methylcytosine; D004247:DNA; D000225:Adenine; D013941:Thymine