Synthesis and properties of trans-3',4'-bridged nucleic acids having typical S-type sugar conformation.
The synthesis of nucleoside analogues with a conformationally restricted sugar moiety is of great interest. The present research describes the synthesis of BNA (bridged nucleic acid) monomers 1 and 2 bearing a 4,7-dioxabicyclo[4.3.0]nonane skeleton and a methoxy group at the C2' position. Conformational analysis showed that the sugar moiety of these monomers is restricted in a typical S-type conformation. It was difficult to synthesize the phosphoramidite derivative of the ribo-type monomer 1, while the phosphoramidite of the arabino-type monomer 2 was successfully prepared and incorporated into oligodeoxynucleotides (ODNs). The hybridization ability of the obtained ODN derivatives containing 2 with complementary strands was evaluated by melting temperature (T(m)) measurements. As a result, the ODN derivatives hybridized with DNA and RNA complements in a sequence-selective manner, though the stability of the duplexes was lower than that of the corresponding natural DNA/DNA or DNA/RNA duplex.
Sekiguchi
Mitsuaki
M
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Obika
Satoshi
S
Harada
Yasuki
Y
Osaki
Tomohisa
T
Somjing
Roongjang
R
Mitsuoka
Yasunori
Y
Shibata
Nao
N
Masaki
Miyuki
M
Imanishi
Takeshi
T
D000577:Amides; D001087:Arabinonucleosides / Q000138:chemical synthesis; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis*; D002236:Carbohydrate Conformation; D002241:Carbohydrates / Q000737:chemistry*; D004247:DNA / Q000378:metabolism; D009691:Nucleic Acid Denaturation; D009693:Nucleic Acid Hybridization; D009696:Nucleic Acids / Q000138:chemical synthesis*; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000378:metabolism; D010756:Phosphoric Acids; D012313:RNA / Q000378:metabolism; D013696:Temperature
D000577:Amides; D001087:Arabinonucleosides; D001952:Bridged-Ring Compounds; D002241:Carbohydrates; D009696:Nucleic Acids; D009838:Oligodeoxyribonucleotides; D010756:Phosphoric Acids; D012313:RNA; D004247:DNA; C011067:phosphoramidic acid