Mitsuaki Sekiguchi

Triplex-forming enhancement with high sequence selectivity by single 2′-O,4′-C-methylene bridged nucleic acid (2′,4′-BNA) modification

Triplex-forming ability of the oligonucleotides containing one 2′-O,4′-C-methyleneribonucleic acid (2′,4′-BNA) unit was investigated by measurement of the melting temperature (Tm), and the 2′,4′-BNA modification promoted the marked triplex stabilization in a highly sequence-selective manner.

Synthesis and conformation of a novel bridged nucleoside with S-type sugar puckering, trans-3′,4′-BNA monomer

Abstract A novel bridged nucleoside bearing a 4,7-dioxabicyclo[4.3.0]nonane skeleton, trans-3′,4′-BNA monomer, was successfully synthesized. A 1H NMR experiment and an X-ray crystallographic analysis revealed that the sugar puckering of the 3′,4′-BNA monomer was restricted to an S-type (C3′-exo) conformation.

Selective recognition of CG interruption by 2′,4′-BNA having 1-isoquinolone as a nucleobase in a pyrimidine motif triplex formation☆

Abstract To develop a novel nucleoside analogue for the effective recognition of CG interruption in a homopurine–homopyrimidine tract of double-stranded DNA (dsDNA), we succeeded in the synthesis of a triplex-forming oligonucleotide (TFO) containing a novel 2′,4′-BNA (Q B ) bearing 1-isoquinolone as a nucleobase, and the triplex-forming ability and sequence-selectivity of the TFO (TFO-Q B ) were examined. On melting temperature ( T m ) measurements, it was found that the TFO-Q B formed a stable triplex DNA in a highly sequence-selective manner under near physiological conditions.

Synthesis and properties of a novel bridged nucleic acid analogue, 5'-amino-3',5'-BNA.

An oligonucleotide P3′⇉N5′ phosphoramidate (5′-amino-DNA) attracts much attention because of its potential for application to DNA sequencing; however, its ability to hybridize with complementary strands is low. To overcome this drawback of the 5′-amino-DNA, we have designed and successfully synthesized a novel nucleic acid analogue having a P3′⇉N5′ phosphoramidate linkage and a constrained sugar moiety, 5′-amino-3′-C,5′-N-methylene bridged nucleic acid (5′-amino-3′,5′-BNA). The binding affinity of the 5′-amino-3′,5′-BNA towards complementary DNA and RNA strands was investigated by UV melting experiments. The melting temperature (Tm) of the duplex comprising the 5′-amino-3′,5′-BNA and its complementary strand was much higher than that of the duplex containing the corresponding 5′-amino-DNA.

Synthesis of Novel 2′-Deoxy Type Trans-3′,4′-Bridged Nucleic Acid

We newly designed and synthesized a 2 ′-deoxy type trans-3′,4′-bridged nucleic acid (trans-3′,4′-BNA) analogues bearing a 4,7-dioxabicyclo[4.3.0]nonane structure. The synthesis of the trans-3′,4′-BNA was carried out successfully from thymidine over 21 steps. The structure of trans-3′,4′-BNA was confirmed by x-ray crystallographic analysis, indicating that the furanose ring has a typical S-type conformation with C3′-exo puckering.