Effect of an N-substituent in sulfonamide-bridged nucleic acid (SuNA) on hybridization ability and duplex structure.
A sulfonamide-bridged nucleic acid without an N-substituent (SuNA[NH]) was successfully synthesized. A comparison of the SuNA[NMe]- and SuNA[NH]-modified oligonucleotides revealed that the duplex-forming abilities of the SuNA[NMe]-modified oligonucleotides with complementary DNA and RNA were higher than those of the SuNA[NH]-modified oligonucleotides. The crystal structures of DNA duplexes containing a SuNA[NR] revealed that the helical structures of the two duplexes and hydration patterns around the bridge moiety were different. These results provide insights into hydration patterns and rationale for the high RNA affinity of SuNA-modified oligonucleotides.
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. obika@phs.osaka-u.ac.jp and Discovery Research Laboratory for Innovative Frontier Medicines, Shionogi & Co., Ltd, 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
Yasunori
Y
Mitsuoka
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. obika@phs.osaka-u.ac.jp.
Hiroshi
H
Aoyama
Discovery Research Laboratory for Innovative Frontier Medicines, Shionogi & Co., Ltd, 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
Akira
A
Kugimiya
Discovery Research Laboratory for Innovative Frontier Medicines, Shionogi & Co., Ltd, 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
Yuko
Y
Fujimura
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. obika@phs.osaka-u.ac.jp.
Tsuyoshi
T
Yamamoto
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. obika@phs.osaka-u.ac.jp.
Reiko
R
Waki
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. obika@phs.osaka-u.ac.jp.
Fumito
F
Wada
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. obika@phs.osaka-u.ac.jp.
Saori
S
Tahara
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. obika@phs.osaka-u.ac.jp.
Motoki
M
Sawamura
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. obika@phs.osaka-u.ac.jp.
Mio
M
Noda
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. obika@phs.osaka-u.ac.jp and Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Nishihama, Yamashiro-cho, Tokushima 770-8514, Japan.
Yoshiyuki
Y
Hari
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. obika@phs.osaka-u.ac.jp.
Satoshi
S
Obika
D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D009584:Nitrogen / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D012313:RNA / Q000737:chemistry* / Q000235:genetics; D013449:Sulfonamides / Q000737:chemistry*
D013449:Sulfonamides; D012313:RNA; D004247:DNA; D009584:Nitrogen