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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.

Mitsuoka Y, Kodama T, Ohnishi R, Hari Y, Imanishi T, Obika S - Nucleic Acids Res. (2009)

Bottom Line: Oligonucleotides (BNA(COC)) containing this monomer show high affinity with complementary single-stranded RNA and significant resistance to nuclease degradation.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.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.

ABSTRACT
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.

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X-ray structure of 2′,4′-BNACOC-A (13).
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Figure 3: X-ray structure of 2′,4′-BNACOC-A (13).

Mentions: The structural features of 2′,4′-BNACOC-A monomer 13 were well confirmed by 1H NMR measurement and X-ray crystallography (Figure 3, Table 4 and also see experimental sections). No scalar coupling between H1′ and H2′ in the 1H NMR spectra of 13 and 22 strongly suggested the North-type (N-type) sugar puckers, as observed in a series of 2′,4′-BNA (LNA). The crystal structure of 2′,4′-BNACOC-A (13) revealed the pseudorotation phase angle P (32°) supporting its N-type sugar pucker and COC linkage configuration surrounded the O3′ atom. Moreover, the νmax and δ values of 13 were 38° and 78°, respectively. These values are in good agreement with the parameters of the C3′-endo structure which is the typical N-type seen in the A-form RNA duplex (4–6).Figure 3.


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.

Mitsuoka Y, Kodama T, Ohnishi R, Hari Y, Imanishi T, Obika S - Nucleic Acids Res. (2009)

X-ray structure of 2′,4′-BNACOC-A (13).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2651773&req=5

Figure 3: X-ray structure of 2′,4′-BNACOC-A (13).
Mentions: The structural features of 2′,4′-BNACOC-A monomer 13 were well confirmed by 1H NMR measurement and X-ray crystallography (Figure 3, Table 4 and also see experimental sections). No scalar coupling between H1′ and H2′ in the 1H NMR spectra of 13 and 22 strongly suggested the North-type (N-type) sugar puckers, as observed in a series of 2′,4′-BNA (LNA). The crystal structure of 2′,4′-BNACOC-A (13) revealed the pseudorotation phase angle P (32°) supporting its N-type sugar pucker and COC linkage configuration surrounded the O3′ atom. Moreover, the νmax and δ values of 13 were 38° and 78°, respectively. These values are in good agreement with the parameters of the C3′-endo structure which is the typical N-type seen in the A-form RNA duplex (4–6).Figure 3.

Bottom Line: Oligonucleotides (BNA(COC)) containing this monomer show high affinity with complementary single-stranded RNA and significant resistance to nuclease degradation.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.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus