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2022
■論文
Development of phosphoramidite reagents for the synthesis of base-labile oligonucleotides modified with a linear aminoalkyl and amino-PEG linker at the 3′-end
T. Osawa, Q. Ren, S. Obika
Molecules, 2022, 27, 8501.
Structure-activity Relationships of Anti-microRNA Oligonucleotides Containing Cationic Guanidine-Modified Nucleic Acids
T. Takegawa-Araki, S. Kumagai, K. Yasukawa, M. Kuroda, T. Sasaki, S. Obika
J. Med. Chem., 2022, 65, 2139–2148.

Synthesis and physical and biological properties of 1,3-diaza-2-oxophenoxazine-conjugated oligonucleotides
R. Yamaji, O. Nakagawa, Y. Kishimoto, A. Fujii, T. Matsumura, T. Nakayama, H. Kamada, T. Osawa, T. Yamaguchi, S. Obika
Bioorg. Med. Chem., 2022, 72, 116972.

Synthesis, duplex-forming ability, and nuclease resistance of oligonucleotides containing a thymidine derivative with a 1-oxaspiro[4.5]decane skeleton
T. Osawa, N. Yano, H. Aoyama, S. Obika
Chem. Pharm. Bull., 2022, 70(10), 699–706.

Conjugation of oligonucleotides with activated carbamate reagents prepared by the Ugi reaction for oligonucleotide library synthesis
R. Kita, T. Osawa, S. Obika
RSC Chem. Biol., 2022, 3(6), 728–738.

Synthesis of Sugar and Nucleoside Analogs and Evaluation of Their Anticancer and Analgesic Potentials
F. Hussain, F. I. Rahman, P. Saha, A. Mikami, T. Osawa, S. Obika and S. M. A. Rahman
Molecules, 2022, 27(11), 3499.

Reduction of Off-Target Effects of Gapmer Antisense Oligonucleotides by Oligonucleotide Extension
H. Yasuhara, T. Yoshida, K. Sasaki, S. Obika, T. Inoue
Mol. Diagn. Ther., 2022, 1, 117.

Physicochemical property evaluation of modification oligonucleotides by traveling-wave ion mobility mass spectrometry
S. Omuro, T. Yamaguchi, T. Kawase, M. Terasaki, K. Hirose, S. Obika
Rapid Commun. Mass Spectrom., 2022, 36, e9279.
■著書
4.3 核酸の分析
大澤昂志、小比賀聡
医薬品開発のための分光法, 2022, 197–206.
2021
■論文
Identification of Potent and Selective Inhibitors of Fat Mass Obesity Associated Protein Using a Fragment-Merging Approach
M. Prakash, Y. Itoh, Y. Fujiwara, Y. Takahashi, Y. Takada, P. Mellini, E. E. Elboray, M. Terao, Y. Yamashita, C. Yamamoto, T. Yamaguchi, M. Kotoku, Y. Kitao, R. Singh, R. Roy, S. Obika, M. Oba, D. O. Wang, T. Suzuki
J. Med. Chem., 2021, 64, 15810/
Synthesis and duplex-forming ability of oligonucleotides modified with 4'-C,5'-C-methylene-bridged nucleic acid (4',5'-BNA)
T. Yamaguchi, C. Yamamoto, M. Horiba, H. Aoyama, S. Obika
Bioorg. Med. Chem., 2021, 46, 116359

Enhanced duplex- and triplex-forming ability and enzymatic resistance of oligodeoxynucleotides modified by a tricyclic thymine derivative
Y. Kishimoto, A. Fujii, O. Nakagawa, S. Obika
Org. Biomol. Chem., 2021, 19, 8063

2′,4′-BNA/LNA with 9-(2-Aminoethoxy)-1,3-diaza-2-oxophenoxazine Efficiently Forms Duplexes and Has Enhanced Enzymatic Resistance
Y. Kishimoto, O. Nakagawa, A. Fujii, K. Yoshioka, T. Nagata, T. Yokota, S. Obika
Chem. Eur. J., 2021,27, 2427

Azobenzene-modified DNA Aptamers Evolved by Capillary Electrophoresis (CE)-SELEX Method
K. Morihiro, O. Hasegawa, Y. Kasahara, S. Mori, T. Kasai, M. Kuwahara, S. Obika
Bioorg. Med. Chem. Lett., 2021, 31, 127607

α-Synuclein Dynamics in Induced Pluripotent Stem Cell-derived Dopaminergic Neurons from a Parkinson’s Disease Patient (PARK4) with SNCA Triplication
H. Fukusumi, K. Togo, M. Sumida, M. Nakamori, S. Obika, K. Baba, T. Shofuda, D. Ito, H. Okano, H. Mochizuki, Y. Kanemura
FEBS Open Bio, 2021, 11, 354

Crystallographic Structure of Novel Types of AgI-Mediated Base Pairs in Non-canonical DNA Duplex Containing 2′-O,4′-C-Methylene Bridged Nucleic Acids
O. Nakagawa, H. Aoyama, A. Fujii, Y. Kishimoto, S. Obika
Chem. Eur. J., 2021, 27, 3842

Design and In Vitro Evaluation of Splice-switching Oligonucleotides Bearing Locked Nucleic Acids, Amido-bridged Nucleic Acids, and Guanidine-bridged Nucleic Acids
T. Shimo, Y. Nakatsuji, K. Tachibana, S. Obika
Int. J. Mol. Sci., 2021, 22, 3526

■著書
各論① 核酸医薬の化学
大澤昂志、小比賀聡
BIO Clinica, 2021, 36, 7

核酸医薬毒性機序概論
三上敦士、小比賀聡
実験医学(増刊:本領を発揮する創薬モダリティ), 2021, 39, 145
2020
■論文
Effect of oligonucleotide structural difference on matrix‐assisted laser desorption/ionization in‐source decay in comparison with collision‐induced dissociation fragmentation
S. Kimura, S. Obika
Rapid Commun. Mass Spectrom, 2020, 34, e8819
Synthesis and evaluation of artificial nucleic acid bearing an oxanorbornane scaffold
H. Komine, S. Mori, K. Morihiro, K. Ishida, T. Okuda, Y. Kasahara, H. Aoyama, T. Yamaguchi, S. Obika
Molecules, 2020, 25, 1732

Different reactivity of Sp and Rp isomers of phosphorothioate-modified oligonucleotides in a duplex structure
M. A. Islam, A. Fujisaka, J. Kawakami, T. Yamaguchi, S. Obika
Bioorg. Med. Chem. Lett., 2020, 30, 127166

Theoretical Analyses and Experimental Validation of The Effects Caused by The Fluorinated Substituent Modification of DNA
J. Koseki, M. Konno, A. Asai, N. Horie, K. Tsunekuni, K. Kawamoto, S. Obika, Y. Doki, M. Mori, H. Ishii
Sci. Rep., 2020, 10, 1138

Synthesis and properties of oligonucleotides having ethynylphosphonate (EP) linkages
M. Horiba, T. Yamaguchi, S. Obika
J. Org. Chem., 2020, 85, 1794

Nucleobase Derivatives Induce In-Source Decay of Oligonucleotides as New MALDI Matrices
S. Kimura, A. Fujisaka, S. Obika
Rapid Commun. Mass Spectrom, 2020, 34, e8620

Synthesis of Selenomethylene-locked Nucleic Acids (SeLNA) Nucleoside Unit Bearing an Adenine Base
Y. Moai, H. Hiroaki, S. Obika, T. Kodama
Nucleosides, Nucleotides, Nucleic Acids, 2020, 39, 131

Effect of Modular Conjugation Strategy for N-Acetylgalactosamine-targeted Antisense Oligonucleotides
T. Yamamoto, M. Sawamura, C. Terada, K. Kashiwada, F. Wada, A. Yamayoshi, S. Obika, M. Harada-Shiba
Nucleosides, Nucleotides, Nucleic Acids, 2020, 39, 109

Oligonucleotides Containing Phenoxazine Artificial Nucleobases: Triplex-Forming Abilities and Fluorescence Properties.
A. Fujii, O. Nakagawa, Y. Kishimoto, Y. Nakatsuji, N. Nozaki, S. Obika
ChemBioChem, 2020, 21, 860

Synthesis and Properties of GuNA Purine/Pyrimidine Nucleosides and Oligonucleotides
Shinji Kumagai, Hiroaki Sawamoto, Tomo Takegawa-Araki, Yuuki Arai, Shuhei Yamakoshi, Katsuya Yamada, Tetsuya Ohta, Eiji Kawanishi, Naohiro Horie, Takao Yamaguchi, Satoshi Obika
Org. Biomol. Chem., 2020, 21, 9461

Base-modified aptamers obtained by cell-internalization SELEX facilitate cellular uptake of an antisense oligonucleotide
K. Tanaka, T. Okuda, Y. Kasahara, S. Obika
Mol. Ther. Nucleic Acids, 2020, 23, 440

Synthesis and properties of oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing adenine, guanine, or 5-methylcytosine nucleobases
Naohiro Horie, Takao Yamaguchi, Shinji Kumagai, Satoshi Obika
Beilstein J. Org. Chem., 2020, 17, 622

Discovery of Cell-internalizing Artificial Nucleic Acid Aptamers for Lung Fibroblasts and Targeted Drug Delivery
H. Uemachi, Y. Kasahara, K. Tanaka, T. Okuda, Y. Yoneda, S. Obika
Bioorg. Chem., 2020, 105, 104321

DNA Polymerase Variants with High Processivity and Accuracy for Encoding and Decoding Locked Nucleic Acid Sequences
H. Hoshino, Y. Kasahara, M. Kuwahara, S. Obika
J. Am. Chem. Soc, 2020, 142, 21530

1. Amido-Bridged Nucleic Acid-Modified Antisense Oligonucleotides Targeting SYT13 to Treat Peritoneal Metastasis of Gastric Cancer
M. Kanda, Y. Kasahara, D. Shimizu, T. Miwa, S. Umeda, K. Sawaki, S. Nakamura, Y. Kodera, S. Obika
Molecular Therapy-Nucleic Acids, 2020, 22, 791

■総説
核酸医薬品の品質評価に関する考え方 -仮想核酸医薬品をモデルにして
滝口 直美、伊藤 浩介、小林 夏季、溝口 潤一、製薬協核酸医薬品質評価タスクフォース、南海 浩一、廣瀬 賢治、笛木 修、佐藤 秀昭、吉田 徳幸、小比賀 聡、井上 貴雄
医薬品医療機器レギュラトリーサイエンス, 2020, 51, 145

核酸医薬品に含まれる不純物の管理に対する考え方
関口 光明、伊藤 浩介、齊藤 隼、滝口 直美、製薬協核酸医薬品質評価タスクフォース、吉田 徳幸、小比賀 聡、井上 貴雄
医薬品医療機器レギュラトリーサイエンス, 2020, 51, 11

Synthesis of Monovalent N‐Acetylgalactosamine Phosphoramidite for Liver‐Targeting Oligonucleotides
T. Yamamoto, C. Terada, K. Kashiwada, A. Yamayoshi, M. Harada-Shiba, S. Obika
Current Protocols in Nucleic Acid Chemistry, 2020, 78, e99

■著書
核酸医薬の原料供給・製造・品質担保に関する課題の抽出とその解決に向けた提言
山口 卓男、井上 貴雄、小比賀 聡
Pharm Tech Japan, 2020, 36, 109

核酸医薬の製造・分析の現状とアウトソーシング
山口 卓男、井上 貴雄、小比賀 聡
Pharm Tech Japan, 2020, 36, 47

(2章2節 糖部修飾核酸)
大澤昂志、小比賀聡
核酸化学ハンドブック

2019
■論文
Inhibiting Guanine Oxidation and Enhancing Excess-electron-transfer Efficiency of A Pyrene-modified Oligonucleotide by Introducing An Electron-donating Group on Pyrene
T. Okuda, Y. Kawashima, Y. Kasahara, T. Takagi, J. Yamamoto, S. Iwai, S. Obika
Chem. Commun., 2019, 55, 14062
Evaluation of Off-target Effects of Gapmer Antisense Oligonucleotides Using Human Cells
T. Yoshida, Y. Naito, K. Sasaki, H. Kawaji, J. Kawai, M. Naito, H. Okuda, S. Obika, T. Inoue
Genes to Cells, 2019, 24, 827

Derivative Synthesis toward Enhancement of the Biophysical Properties of 2′,4′-Bridged Nucleic Acids
T. Yamaguchi, S. Obika
J. Synth. Org. Chem., 2019, 77, 994

Synthesis of 2′-C,4′-C-Methyleneoxy-bridged Thymidine Derivatives and Properties of Modified Oligonucleotides
T. Osawa, H. Kim, M. Shoji, M. Saijo, M. Dohi, Y. Ito, S. Obika, Y. Hari
J. Org. Chem., 2019, 21, 13336

GREB1 Induced by Wnt Signaling Promotes Development of Hepatoblastoma by Suppressing TGFβ Signaling
S. Matsumoto, T. Yamamichi, K. Shinzawa, Y. Kasahara, S. Nojima, T. Kodama, S. Obika, T. Takehara, E. Morii, H. Okuyuama, A. Kikuchi
Nat. Commun., 2019, 10, 3882

Highly Efficient Silencing of microRNA by Heteroduplex Oligonucleotides
K. Yoshioka, T. Kunieda, Y. Asami, H. Guo, H. Miyata, K. Yoshida Tanaka, Y. Sujino, W. Piao, H. Kuwahara, K. Nishina, R. Hara, T. Nagata, S. Obika, T. Wada, T. Yokota
Nucleic Acids Res., 2019, 47, 7321

A Hydrogen Peroxide-activatable Gemcitabine Prodrug for The Selective Treatment of Pancreatic Ductal Adenocarcinoma
K. Matsushita, T. Okuda, S. Mori, M. Konno, H. Eguchi, A. Asai, J. Koseki, Y. Iwagami, D. Yamada, H. Akita, T. Asaoka, T. Noda, K. Kawamoto, K. Gotoh, S. Kobayashi, Y. Kasahara, K. Morihiro, T. Satoh, Y. Doki, M. Mori, H. Ishii, S. Obika
ChemMedChem, 2019, 14, 1384

Amido-bridged Nucleic Acid (AmNA)-modified Antisense Oligonucleotides Targeting α-Synuclein as A Novel Therapy for Parkinson’s Disease
T. Uehara, C.-J. Choong , M. Nakamori, H. Hayakawa, K. Nishiyama, Y. Kasahara, K. Baba, T. Nagata, T. Yokota, H. Tsuda, S. Obika, H. Mochizuki
Sci. Rep., 2019, 9, 7567

A Gapmer Antisense Oligonucleotide Targeting SRRM4 Is a Novel Therapeutic Medicine for Lung Cancer
M. Shimojo, Y. Kasahara, M. Inoue, S. Tsunoda, Y. Shudo, T. Kurata, S. Obika
Sci. Rep., 2019, 9, 7618

Enhancement of exon skipping activity by reduction in secondary structure content of LNA-based splice-switching oligonucleotides
T. Shimo, K. Tachibana, Y. Kawawaki, Y. Watahiki, T. Ishigaki, Y. Nakatsuji, T. Hara, J. Kawakami, S. Obika
Chem. Commun., 2019, 55, 6850-6853

Thymidine, 2-Thiothymidine, and 2-Selenothymidine: Comparison of Mismatch Discriminations
T. Habuchi, T. Yamaguchi, S. Obika
Heterocycles, 2019, 48, 832-837

1,3,9‐Triaza‐2‐Oxophenoxazine Artificial Nucleobase Forms Highly Stable Self‐base Pairs with Three AgI Ions in a Duplex
A. Fujii, O. Nakagawa, Y. Kishimoto, T. Okuda, Y. Nakatsuji, N. Nozaki, Y. Kasahara, S. Obika
Chem. Eur. J., 2019, 25, 7443-7448

Thioamide-bridged Nucleic Acid (thioAmNA) Bearing Thymine or 2-Thiothymine: Duplex Forming Ability, Base Discrimination, and Enzymatic Stability
T. Habuchi, T. Yamaguchi, S. Obika
ChemBioChem, 2019, 20, 1-9

Effective syntheses of 2’,4’-BNANC monomers bearing adenine, guanine, thymine, and 5-methylcytosine, and the properties of oligonucleotides fully modified with 2′,4′-BNANC
A. Fujisaka, Y. Hari, H. Takuma, S.M.A. Rahman, H. Yoshikawa, J. Pang, T. Imanishi, S. Obika
Bioorg. Med. Chem., 2019, 27, 1728–1741

Detection of Esterase Activity by Chromogenic and Fluorogenic Probe Based on an O-Nitrobenzoxadiazole (O-NBD) Unit
K. Okada, T. Yamaguchi, K. Dodo, M. Sodeoka, S. Obika
Bioorg. Med. Chem., 2019, 27, 1444–1448

Chemically Modified Antisense Oligonucleotide Against ARL4C Inhibits Primary and Metastatic Liver Tumor Growth
T. Harada, S. Matsumoto, S. Hirota, H. Kimura, S. Fujii, Y. Kasahara, H. Gon, T. Yoshida, T. Itoh, N. Haraguchi, T. Mizushima, T. Noda, H. Eguchi, S. Nojima, E. Morii, T. Fukumoto, S. Obika, A. Kikuchi
Mol. Cancer Ther., 2019, 18, 602

Hybridization and Mismatch Discrimination Abilities of 2′,4′-Bridged Nucleic Acids Bearing 2-Thiothymine or 2-Selenothymine Nucleobase
T. Habuchi, T. Yamaguchi, H. Aoyama, M. Horiba, K. Ito, S. Obika
J. Org. Chem., 2019, 84, 1430-1439

High-Contrast Facile Imaging with Target-Directing Fluorescent Molecular Rotors N3-Modified Thioflavin T Derivatives
Y. Kataoka, H. Fujita, A. Afanasyeva, C. Nagao, K. Mizuguchi, Y. Kasahara, S. Obika, M. Kuwahara
Biochemistry, 2019, 58, 493

■総説
Synthesis of Monovalent N‐Acetylgalactosamine Phosphoramidite for Liver‐Targeting Oligonucleotides
T. Yamamoto, C. Terada, K. Kashiwada, A. Yamayoshi, M. Harada-Shiba, S. Obika
Current Protocols in Nucleic Acid Chemistry, 2019, 78, e99

■著書
有機化学的に修飾した核酸の有用性
梅本 忠士、小比賀 聡
医学のあゆみ, 2019, 第269巻, 5号 397

核酸医薬の化学修飾
森廣 邦彦、小比賀 聡
Medical Science Digest, 2019, 45

アンチセンス核酸医薬の開発動向—作用メカニズムから分子設計戦略まで
山口 卓男、小比賀 聡
実験医学(特集:なぜ、いま核酸医薬なのか 次なる創薬モダリティの本命), 2019, 37, 8–14

2018
■論文
2′-O,4′-C-Methylene-bridged Nucleic Acids Stabilize Metal-mediated Base Pairing in A DNA Duplex
O. Nakagawa, A. Fujii, Y. Kishimoto, Y. Nakatsuji, N. Nozaki, S. Obika
ChemBioChem, 2018, 19, 2372-2379.
Development of A Detection Method for Antisense Oligonucleotides in Mouse Kidneys by MALDI Imaging Mass Spectrometry
H. Yokoi, Y. Kasahara, S. Obika, T. Doi, H. Kamada
Rapid Commun. Mass Spectrom., 2018, 32, 1984-1990.

Facil synthesis and fundamental properties of an N–methylguanidine–bridged nucleic acid (GuNA[NMe])
N. Horie, S. Kumagai, Y. Kotobuki, T. Yamaguchi, S. Obika
Org. Biomol. Chem., 2018, 16, 6531-6536

Development of oligonucleotide-based antagonists of Ebola virus protein 24 inhibiting its interaction with karyopherin alpha 1
K. Tanaka, Y. Kasahara, Y. Miyamoto, O. Takumi, T. Kasai, K. Onodera, M. Kuwahara, M. Oka, Y. Yoneda, S. Obika
Org. Biomol. Chem., 2018, 16, 4456-4463

Synthesis and biophysical properties of 5’-thio-2’,4’-BNA/LNA oligonucleotide
M. A. Islam, A. Fujisaka, S. Mori, K. R. Ito, T. Yamaguchi, S. Obika
Bioorg. Med. Chem., 2018, 26, 3634-3638

Construction of a tri-chromatic reporter cell line for the rapid and simple screening of splice-switching oligonucleotides targeting DMD exon 51 using high content screening
T. Shimo, K. Tachibana, S. Obika
PLoS ONE, 2018, 13(5), e0197373

Effective Gene Silencing Activity of Prodrug-type 2’-O-Methyldithiomethyl siRNA Compared with Non-prodrug-type 2’-O-Methyl siRNA
J. Hayashi, M. Nishigaki, Y. Ochi, S. Wada, F. Wada, O. Nakagawa, S. Obika, M. Harada-Shiba, H. Urata
Bioorg. Med. Chem. Lett., 2018, 28, 2171-2174

Estimated Number of Off-target Candidate Sites for Antisense Oligonucleotides in Human mRNA Sequences
T. Yoshida, Y. Naito, K. Sasaki, E. Uchida, Y. Sato, M. Naito, T. Kawanishi, S. Obika, T. Inoue
Genes to Cells, 2018, 23, 448-455

Generation of splice switching oligonucleotides targeting the Cockayne syndrome group B gene product in order to change the diseased cell state
Y. Sin, F. Makimura, M. Saijo, S. Obika
Biochem. Biophys. Res. Commun., 2018, 500(2), 163-169

Synthetic Method for 2’-Amino-LNA Bearing Any of the Four Nucleobases via a Transglycosylation Reaction
H. Sawamoto, Y. Arai, S. Yamakoshi, S. Obika, E. Kawanishi
Org. Lett., 2018, 20, 1928-1931

Cholesterol-GalNAc Dual Conjugation Strategy for Reducing Renal Distribution of Antisense Oligonucleotides
F. Wada, T. Yamamoto, T. Ueda, M. Sawamura, S. Wada, M. Harada-Shiba, S. Obika
Nucleic Acid Ther., 2018, 28, 50-57

Hydrogen peroxide-triggered gene silencing in mammalian cells through boronated antisense oligonucleotides
S. Mori, K. Morihiro, T. Okuda, Y. Kasahara, S. Obika
Chem. Sci., 2018, 9, 1112-1118

A Novel Human Muscle Cell Model of Duchenne Muscular Dystrophy Created by CRISPR/Cas9 and Evaluation of Antisense-Mediated Exon Skipping
T. Shimo, K. Hosoki, Y. Nakatsuji, T. Yokota, S. Obika
J. Hum. Genet., 2018, 63, 365-375

Synthesis and Properties of Oligonucleotides Containing 3′-O,4′-C-Ethyleneoxy-bridged 5-Methyluridines
T. Osawa, Y. Hitomi, S. Wakita, H. Kim, M. Dohi, M. Horiba, Y. Ito, S. Obika, Y. Hari
Heterocycles, 2018, 97, 306-313

■総説
進む核酸医薬品の開発
小比賀 聡
現代化学, 東京化学同人, 2018, 572, 50-55

核酸医薬品の安全性評価に関する考え方 -仮想核酸医薬品をモデルにして -第3回:既存情報の有効活用
木下 潔、真木 一茂、荒戸 照世、太田 哲也、小野寺 博志、佐藤 秀昭、中澤 隆弘、平林 容子、笛木 修、三井田 宏明、吉田 徳幸、渡部 一人、小比賀 聡、井上 貴雄
医薬品医療機器レギュラトリーサイエンス, 2018, 49, 207-214.

核酸医薬品の安全性評価に関する考え方 -仮想核酸医薬品をモデルにして -第2回:局所投与剤の毒性評価
木下 潔、真木 一茂、荒戸 照世、太田 哲也、小野寺 博志、佐藤 秀昭、中澤 隆弘、平林 容子、笛木 修、三井田 宏明、吉田 徳幸、渡部 一人、小比賀 聡、井上 貴雄
医薬品医療機器レギュラトリーサイエンス, 2018, 49, 157-163.

核酸医薬品の安全性評価に関する考え方 -仮想核酸医薬品をモデルにして -第1回:オンターゲット毒性の評価
木下 潔、真木 一茂、荒戸 照世、太田 哲也、小野寺 博志、佐藤 秀昭、中澤 隆弘、平林 容子、笛木 修、三井田 宏明、吉田 徳幸、渡部 一人、小比賀 聡、井上 貴雄
医薬品医療機器レギュラトリーサイエンス, 2018, 49, 105-111.

核酸医薬の糖部および塩基部に対する化学修飾
小比賀 聡
最新医学, 2018, 73, 760-767.

■著書
Synthesis of Therapeutic Oligonucleotides
S. Obika, M. Sekine
Springer 2018
DOI:10.1007/978-981-13-1912-9

Optimization of 2′,4′-BNA/LNA-Based Oligonucleotides for Splicing Modulation In Vitro
T. Shimo, S. Obika
Methods Mol Biol., 2018, 1828, 395-411

2017
■論文
Antisense Oligonucleotides Targeting Y-Box Binding Protein-1 Inhibit Tumor Angiogenesis by Downregulating Bcl-xL-VEGFR2/-Tie Axes
K. Setoguchi, L. Cui, N. Hachisuka, S. Obchoei, K. Shinkai, F. Hyodo, K. Kato, F. Wada,T. Yamamoto, M. Harada-Shiba, S. Obika, K. Nakano
Molecular Therapy-Nucleic Acids, 2017, 9, 170-181.
Synthesis and thermal stabilities of oligonucleotides containing 2’-O,4’-C-methylene bridged nucleic acid with a phenoxazine base.
Y. Kishimoto, A. Fujii, O. Nakagawa, T. Nagata, T. Yokota, Y. Hari, S. Obika
Org. Biomol. Chem. 2017;38(15):8145-8152
DOI:10.1039/C7OB01874F

Small Nucleolar Noncoding RNA SNORA23, Upregulated in Human Pancreaic Ductal Adenocarcinoma, Regulates Expression of SYNE2 to Promote Growth and Metastasis of Xenograft Tumors in Mice.
L. Cui, K. Nakano, S. Obchoei, K. Setoguchi, M. Matsumoto, T. Yamamoto, S. Obika, K. Shimada, N. Hiraoka
Gastroenterogy 2017 July;153:292-306

Synthesis, duplex-forming ability, enzymatic stability, and in vitro antisense potency of oligonuclreotides including 2’-C, 4’-C-ethyleneoxy-bridged thymedine derivatives.
T. Osawa, M. Sawamura, F. Wada, T. Yamamoto, S. Obika, Y.Hari
Org. Biomol. Chem. 2017 May;15(18):3955-3963

Synthesis of the 5-Methyluridine Monomer of 3’-O,4’-C-Ethyleneoxy-bridged Nucleic Acid.
T. Osawa, M. Dohi, Y. Hitomi, Y. Ito, S. Obika, Y. Hari
Heterocycles. 2017;95(1):342-352

Phospholamban Inhibition by a Single Dose of Locked Nucleic Acid Antisense Oligonucleotide Improves Cardiac Contractility in Pressure Overload-Induced Systolic Dysfunction in Mice.
H. Morihara, T, Yamamoto, H. Oiwa, K. Tonegawa, D. Tsuchiyama, I. Kawakatsu, M. Obana, M. Maeda, T. Mohri, S. Obika, Y Fujio, H. Nakayama
J. Cardiovasc. Pharmacol. Ther. 2017 May;22(3):273-282

Evaluation of size-exclusion chromatography for the analysis of phosphorothioate oligonucleotides.
A. Shimoyama, A. Fujisaka, S. Obika.
J. Pharm. Biomed. Anal. 2017 Mar. 20;136:55-65

Synthesis and Properties of 7-Deazapurine- and 8-Aza-7-deazapurine-Locked Nucleic Acid Analogues: Effect of the Glycosidic Torsion Angle.
T. Hara, T. Kodama, Y. Takegaki, K. Morihiro, K. R. Ito, S. Obika
J. Org. Chem. 2017;82(1):25-36

Triazole- and Tetrazole-Bridged Nucleic Acids: Synthesis, Duplex Stability, Nuclease Resistance, and in Vitro and in Vivo Antisense Potency.
Y. Mitsuoka, T. Yamamoto, A. Kugimiya, R. Waki, F. Wada, S. Tahara, M. Sawamura, M. Noda, Y. Fujimura, Y. Kato, Y. Hari, S. Obika
J. Org. Chem. 2017 Jan. 6;82(1):12-24
■総説
核酸医薬品の現状と品質管理に関わるレギュラトリーサイエンス上の課題
藤坂 朱紀、伊藤 浩介、小比賀 聡
レギュラトリーサイエンス学会誌, 2017, 7, 113-120.

Recent Advances in Medicinal Chemistry of Antisense Oligonucleotides
K. R. Ito, S. Obika
Comprehensive Medicinal Chemistry III, Elsevier, 2017, p216-232.

核酸医薬開発における化学
小比賀 聡、笠原 勇矢
日本発次世代創薬のための化学, 2017, 70-1, 020-022, 化学と工業

Biological Applications of Xeno Nucleic Acids.
K. Morihiro, Y. Kasahara, S. Obika
Mol. Biosyst. 2017 Jan. 31;13(2):235-245
■著書
Designing Effective Antisense Oligonucleotides for Exon Skipping.
T. Shimo, R. Maruyama, T. Yokota
Methods Mol Biol. 2017;1687:143-155
DOI:10.1007/978-1-4939-7374-3_10
2016
■論文
Systematic Evaluation of Biophysical and Functional Characteristics of Selenomethylene-Locked Nucleic Acid-Mediated Inhibition of miR-21.
S. Nahar, A. Singh, K. Morihiro, Y. Moai, T. Kodama, S. Obika, S. Maiti.
Biochemistry. 2016 Dec. 20;55(50):7023-32.
In vitro and in vivo biophysical properties of oligonucleotides containing 5'-thio nucleosides.
M.A. Islam, R. Waki, A. Fujisaka, K.R. Ito, S. Obika.
Drug Discov. Ther. 2016;10(5):263-70.

Synthesis of scpBNA-mC, -A, and -G Monomers and Evaluation of the Binding Affinities of scpBNA-Modified Oligonucleotides toward Complementary ssRNA and ssDNA.
M. Horiba, T. Yamaguchi, S. Obika.
J Org. Chem. 2016 Nov. 18;81(22):11000-8.

Synthesis and properties of novel 2'-C,4'-C-ethyleneoxy-bridged 2'-deoxyribonucleic acids with exocyclic methylene groups.
T. Osawa, S. Obika, Y. Hari.
Org. Biomol. Chem. 2016 Oct. 12;14(40):9481-4.

Synthesis and Properties of 4-(Diarylmethylene)imidazolinone-conjugated Fluorescent Nucleic Acids
T. Okuda, S. Mori, Y. Kasahara, K. Morihiro, M. Ikejiri, K. Miyashita, S. Obika.
Tetrahedron Lett. 2016 July 20;57:3129-32.

Nuclear expression of Y-box binding protein-1 is associated with poor prognosis in patients with pancreatic cancer and its knockdown inhibits tumor growth and metastasis in mice tumor models.
K. Shinkai, K. Nakano, L. Cui, Y. Mizuuchi, H. Onishi, Y. Oda, S. Obika, M. Tanaka, M. Katano.
Int. J. Cancer. 2016 July 15;139(2):433-45.

Effect of an N-substituent in sulfonamide-bridged nucleic acid (SuNA) on hybridization ability and duplex structure.
Y. Mitsuoka, H. Aoyama, A. Kugimiya, Y. Fujimura, T. Yamamoto, R. Waki, F. Wada, S. Tahara, M. Sawamura, M. Noda, Y. Hari, S. Obika.
Org. Biomol. Chem. 2016 July 6;14(27):6531-8.

Evaluation of the effects of chemically different linkers on hepatic accumulations, cell tropism and gene silencing ability of cholesterol-conjugated antisense oligonucleotides.
S. Wada, H. Yasuhara, F. Wada, M. Sawamura, R. Waki, T. Yamamoto, M. Harada-Shiba, S. Obika.
J. Control. Release. 2016 Mar. 28;226:57-65.

Crystal structure of a 2',4'-BNANC[N-Me]-modified antisense gapmer in complex with the target RNA.
J. Kondo, Y. Nomura, Y. Kitahara, S. Obika, H. Torigoe.
Chem. Commun. 2016 Jan. 28;52(11):2354-7.

Wavelength-selective light-triggered strand exchange reaction.
K. Morihiro, T. Kodama, S. Mori, S. Tsunoda, S. Obika.
Org. Biomol. Chem. 2016 Jan. 27;14(5):1555-8.

Consecutive incorporation of functionalized nucleotides with amphiphilic side chains by novel KOD polymerase mutant.
H. Hoshino, Y. Kasahara, H. Fujita, M. Kuwahara, K. Morihiro, S. Tsunoda, S. Obika.
Bioorg. Med. Chem. Lett. 2016 Jan. 15;26(2):530-3.

Serial incorporation of a monovalent GalNAc phosphoramidite unit into hepatocyte-targeting antisense oligonucleotides.
T. Yamamoto, M. Sawamura, F. Wada, M. Harada-Shiba, S. Obika.
Bioorg. Med. Chem. 2016 Jan. 1;24(1):26-32.

■総説
核酸医薬品開発における修飾核酸
(The modified oligonucleotides for nucleic acid drug discovery)
藤坂 朱紀、小比賀 聡
Medical Science Digest 2016 Sep.;42(10):22-5.

Design of antisense oligonucleotides.
S. Obika, Y. Kasahara.
Nihon Yakurigaku Zasshi. 2016 Aug.;148(2):100-4.

化学的アプローチを駆使した核酸医薬の最前線
小比賀 聡、中川 治
今、着実に実り始めた遺伝子治療(遺伝子医学MOOK30), メディカルドゥ, 2016 Jun. 20, 125-31

Synthesis and Properties of 2',4'-Bridged Nucleic Acids Containing Multiple Heteroatoms in the Bridges
Y. Hari, S. Obika.
J. Syn. Org. Chem., Jpn., 2016 Mar. 22, 74, 141-53.

■著書
ヌクレオシドおよび核酸塩基アナログを有する代表的医薬品を列挙し、化学構造に基づく性質について説明できる(第11章 SBO27)
藤坂 朱紀、小比賀 聡
スタンダード薬学シリーズⅡ3, 化学系薬学Ⅱ. 生体分子・医薬品の化学による理解, 日本薬学会(編), 2016, 225-31, 東京化学同人

糖部架橋型核酸の新たな展開(第4章)
小比賀 聡
核酸医薬の創製と応用展開, 和田 猛(監), 2016, 29-39, シーエムシー出版

2015
■論文
Synthesis and Properties of the 5-Methyluridine Derivative of 3,4-Dihydro-2H-pyran-Bridged Nucleic Acid (DpNA).
Osawa T, Hari Y, Dohi M, Matsuda Y, Obika S.
J Org Chem. 2015 Nov 6;80(21):10474-81.
Ca2+ enrichment in culture medium potentiates effect of oligonucleotides.
Hori S, Yamamoto T, Waki R, Wada S, Wada F, Noda M, Obika S.
Nucleic Acids Res. 2015 Oct 30;43(19):e128.

XRN2 is required for the degradation of target RNAs by RNase H1-dependent antisense oligonucleotides.
Hori S, Yamamoto T, Obika S.
Biochem Biophys Res Commun. 2015 Aug 21;464(2):506-11.

DNA/RNA heteroduplex oligonucleotide for highly efficient gene silencing.
Nishina K, Piao W, Yoshida-Tanaka K, Sujino Y, Nishina T, Yamamoto T, Nitta K, Yoshioka K, Kuwahara H, Yasuhara H, Baba T, Ono F, Miyata K, Miyake K, Seth PP, Low A, Yoshida M, Bennett CF, Kataoka K, Mizusawa H, Obika S, Yokota T.
Nat Commun. 2015 Aug 10;6:7969.

Polymerase incorporation of a 2'-deoxynucleoside-5'-triphosphate bearing a 4-hydroxy-2-mercaptobenzimidazole nucleobase analogue.
Morihiro K, Hoshino H, Hasegawa O, Kasahara Y, Nakajima K, Kuwahara M, Tsunoda S, Obika S.
Bioorg Med Chem Lett. 2015 Aug 1;25(15):2888-91.

Synthesis and properties of 2'-O,4'-C-spirocyclopropylene bridged nucleic acid (scpBNA), an analogue of 2',4'-BNA/LNA bearing a cyclopropane ring.
Yamaguchi T, Horiba M, Obika S.
Chem Commun (Camb). 2015 Jun 14;51(47):9737-40.

C5-azobenzene-functionalized locked nucleic acid uridine: isomerization properties, hybridization ability, and enzymatic stability.
Morihiro K, Hasegawa O, Mori S, Tsunoda S, Obika S.
Org Biomol Chem. 2015 May 14;13(18):5209-14.

Amido-bridged nucleic acids with small hydrophobic residues enhance hepatic tropism of antisense oligonucleotides in vivo
Tsuyoshi Yamamoto, Aiko Yahara, Reiko Waki, Hidenori Yasuhara, Fumito Wada, Mariko Harada-Shiba and Satoshi Obika *
Org. Biomol. Chem., 2015 Mar 11;13(12):3757-65.

Synthesis and hybridization property of a boat-shaped pyranosyl nucleic acid containing an exocyclic methylene group in the sugar moiety
Mori, Kazuto; Kodama, Tetsuya; Obika, Satoshi.
Bioorg Med Chem. 2015 Jan 1;23(1):33-7.

In vitro selection of DNA-based aptamers that exhibit RNA-like conformations using a chimeric oligonucleotide library that contains two different xeno-nucleic acids.
Hagiwara K, Fujita H, Kasahara Y, Irisawa Y, Obika S, Kuwahara M.
Mol Biosyst. 2015 Jan;11(1):71-6.

MicroRNAs Induce Epigenetic Reprogramming and Suppress Malignant Phenotypes of Human Colon Cancer Cells.
Ogawa H, Wu X, Kawamoto K, Nishida N, Konno M, Koseki J, Matsui H, Noguchi K, Gotoh N, Yamamoto T, Miyata K, Nishiyama N, Nagano H, Yamamoto H, Obika S, Kataoka K, Doki Y, Mori M, Ishii H.
PLoS One. 2015 May 13;10(5):e0127119.

Polymerase-mediated high-density incorporation of amphiphilic functionalities into DNA: Enhancement of nuclease resistance and stability in human serum
Fujita H, Nakajima K, Kasahara Y, Ozaki H, Kuwahara M.
Bioorg Med Chem Lett. 2015 Jan 15;25(2):333-6.

■総説


2014
■論文
Sulfonamide-bridged nucleic acid: synthesis, high RNA selective hybridization, and high nuclease resistance.
Mitsuoka Y, Fujimura Y, Waki R, Kugimiya A, Yamamoto T, Hari Y, Obika S.
Org. Lett. 2014 Nov 7;16(21):5640-3.
Synthesis of oligonucleotides containing N,N-disubstituted 3-deazacytosine nucleobases by post-elongation modification and their triplex-forming ability with double-stranded DNA.
Akabane-Nakata M, Obika S, Hari Y.
Org. Biomol Chem. 2014 Nov 28;12(44):9011-5.

Kinetic study of the binding of triplex-forming oligonucleotides containing partial cationic modifications to double-stranded DNA.
Hari Y, Ijitsu S, Akabane-Nakata M, Yoshida T, Obika S.
Bioorg Med Chem Lett. 2014 Jul 15;24(14):3046-9.

Target gene knockdown by 2',4'-BNA/LNA antisense oligonucleotides in zebrafish.
toh M, Nakaura M, Imanishi T, Obika S.
Nucleic Acid Ther. 2014 Jun;24(3):186-91.

Guanidine bridged nucleic acid (GuNA): an effect of a cationic bridged nucleic acid on DNA binding affinity.
Shrestha AR, Kotobuki Y, Hari Y, Obika S.
Chem Commun (Camb). 2014 Jan 18;50(5):575-7.

Minimal thioflavin T modifications improve visual discrimination of Guanine-quadruplex topologies and alter compound-induced topological structures.
Kataoka Y, Fujita H, Kasahara Y, Yoshihara T, Tobita S, Kuwahara M.
Anal Chem. 2014 Dec 16;86(24):12078-84.

Synthesis and Characterization of Benzylidene Acetal-Type Bridged Nucleic Acids (BA-BNA).
Kodama T, Morihiro K, Obika S.
Curr Protoc Nucleic Acid Chem. 2014 Sep 8;58:1.31.1-1.31.22.

Design and evaluation of locked nucleic acid-based splice-switching oligonucleotides in vitro
Takenori Shimo, Keisuke Tachibana, Kiwamu Saito, Tokuyuki Yoshida, Erisa Tomita, Reiko Waki, Tsuyoshi Yamamoto, Takefumi Doi, Takao Inoue, Junji Kawakami and Satoshi Obika
Nucleic Acids Research, 2014, 42(12):8174-87.

C5-Azobenzene-substituted 2'-Deoxyuridine-containing Oligodeoxynucleotides for Photo-Swotching Hybridization
Shohei Mori, Kunihiko Morihiro,* Satoshi Obika*
Molecules, 2014, 19, 5109-5118.

Evaluation of Multiple-Turnover Capability of Locked Nucleic Acid Antisense Oligonucleotides in Cell-Free RNase H-Mediated Antisense Reaction and in Mice
Tsuyoshi Yamamoto, Naoko Fujii, Hidenori Yasuhara, Shunsuke Wada, Fumito Wada, Naoya Shigesada, Mariko Harada-Shiba and Satoshi Obika
Nucleic Acid Ther. 2014 Aug;24(4):283-90.

Light-triggered strand exchange reaction using the change in the hydrogen bonding pattern of a nucleobase analogue
Kunihiko Morihiro, Tetsuya Kodama, Reiko Waki and Satoshi Obika
Chem. Sci., 2014, 5, 744-750

The Ability of 1-Aryltriazole-containing Nucleobases to Recognize a TA Base Pair in Triplex DNA
Y. Hari,* M. Nakahara, S. Ijitsu, S. Obika*
Heterocycles, 2014, 88, 377-386

Photoinduced Changes in Hydrogen Bonding Patterns of 8-Thiopurine Nucleobase Analogues in a DNA Strand
Kunihiko Morihiro, Tetsuya Kodama, Shohei Mori, Satoshi Obika*
Org. Biomol. Chem., 2014, 12, 2468.

Locked nucleic acid antisense inhibitor targeting apolipoprotein C-III efficiently and preferentially removes triglyceride from large very low-density lipoprotein particles in murine plasma.
T. Yamamoto, S. Obika, M. Nakatani, H. Yasuhara, F. Wada, M. Shibata, M. Shiba
Eur. J. Pharmacol., 2014, 723, 353-359.
■総説
Development of External Stimuli-responsive Nucleic Acids by Sugar, Backbone, and Nucleobase Modification
Kunihiko Morihiro, Tetsuya Kodama, Satoshi Obika*
Synlett, 2014, 25, 1499-1510.

Synthesis and Characterization of Benzylidene Acetal Type Bridged Nucleic Acids (BA-BNA)
Tetsuya Kodama, Kunihiko Morihiro, Satoshi Obika*
Curr Protoc Nucleic Acid Chem. 2014 Sep 8;58:1.31.1-1.31.22.
2013
■論文
Triplex-forming ability of oligonucleotides containing 1-aryl-1,2,3-triazole nucleobases linked via a two atom-length spacer
Hari, Yoshiyuki; Nakahara, Motoi; Obika, Satoshi
Bioorg. Med. Chem., 2013, 21, 5583-5588
Synthesis of novel polyesteramine dendrimers by divergent and convergent methods
Hitoshi Akiyama, Kazuyuki Miyashita, Yoshiyuki Hari, Satoshi Obika, , Takeshi Imanishi
Tetrahedron, 2013, 69, 6810-6820

Base-pair recognition ability of hydroxyphenyl nucleobases in parallel triplex DNA
Yoshiyuki Hari, , Satoshi Kashima, Hiroyasu Inohara, Shin Ijitsu, Takeshi Imanishi, Satoshi Obika
Tetrahedron, 2013, 69, 6381-6391

Synthesis and Properties of 2 '-O,4 '-C-Ethyleneoxy Bridged 5-Methyluridine
Yoshiyuki Hari *, Tomohiko Morikawa , Takashi Osawa , and Satoshi Obika *
Org. Lett., 2013, 15, 3702-3705

Synthesis and properties of thymidines with six-membered amide bridge
Yoshiyuki Hari, Takashi Osawa, Yutaro Kotobuki, Aiko Yahara, Ajaya R. Shrestha, Satoshi Obika
Bioorg. Med. Chem., 2013, 21, 4405-4412

Capillary Electrophoresis-Systematic Evolution of Ligands by Exponential Enrichment Selection of Base- and Sugar-Modified DNA Aptamers: Target Binding Dominated by 2 '-O,4 '-C-Methylene-Bridged/Locked Nucleic Acid Primer
Yuuya Kasahara, Yuuta Irisawa, Hiroto Fujita, Aiko Yahara, Hiroaki Ozaki, Satoshi Obika, and Masayasu Kuwahara *
Anal. Chem., 2013, 85, 4961-4967

2 ',4 '-BNA/LNA aptamers: CE-SELEX using a DNA-based library of full-length 2 '-O,4 '-C-methylene-bridged/linked bicyclic ribonucleotides
Yuuya Kasahara, Yuuta Irisawa, Hiroaki Ozaki, Satoshi Obika, Masayasu Kuwahara
Bioorg. Med. Chem. Lett., 2013, 23, 1288-1292

2 ',4 '-BNA bearing a chiral guanidinopyrrolidine-containing nucleobase with potent ability to recognize the CG base pair in a parallel-motif DNA triplex
Hari, Yoshiyuki; Akabane, Masaaki; Obika, Satoshi
Chem. Commun., 2013, 49, 7421-7423

Selenomethylene Locked Nucleic Acid Enables Reversible Hybridization in Response to Redox Changes
K. Morihiro, T. Kodama, Kentefu, Y. Moai, R. N. Veedu, S. Obika*
Angew. Chem. Int. Ed. 2013, 52, 5074-5078
■総説
Towards the Sequence-Selective Recognition of Double-Stranded DNA Containing Pyrimidine-Purine Interruptions by Triplex-Forming Oligonucleotides
Y. Hari, S. Obika, T. Imanishi
Eur. J. Org. Chem., 2012, 2875-2887.

医薬・診断薬への応用に向けた化学修飾核酸アプタマーの開発
桑原 正靖、小比賀 聡
化学工業, 2012, 63, 42-48.

糖部架橋型核酸の医薬への応用
小比賀 聡
医薬ジャーナル, 2012, 48, 65-69.
2012
■論文
A 2-AMINO-6-METHYLPYRIDIN-5-YL NUCLEOBASE FOR GC BASE PAIR RECOGNITION IN THE PARALLEL TRIPLEX DNA
Motoi Nakahara, Yoshiyuki Hari,* and Satoshi Obika
HeteroCycles. 2012,Vol 86, No. 2, pp.1135-1146
Synthesis and duplex-forming ability of oligonucleotides containing 4'-carboxythymidine analogs
Y. Hari, T. Osawa, S. Obika
Org. Biomol. Chem., 2012,10, 9639-9649

Superior Silencing by 2′,4′-BNANC-Based Short Antisense Oligonucleotides Compared to 2′,4′-BNA/LNA-Based Apolipoprotein B Antisense Inhibitors
Tsuyoshi Yamamoto, Hidenori Yasuhara, Fumito Wada, Mariko Harada-Shiba, Takeshi Imanishi, and Satoshi Obika
Journal of Nucleic Acids, 2012, Article ID 707323, 7 pages.

Synthesis of Selenomethylene-Locked Nucleic Acid (SeLNA)-Modified Oligonucleotides by Polymerases
M. Wheeler, A. Chardon, A. Goubet, K. Morihiro, S. Y. Tsan, S. Edwards, T. Kodama, S. Obika, R. N. Veedu
Chem. Commun., 2012, 48, 11020-11022.

Development of a 2',4'-BNA/LNA Based siRNA for Dyslipidemia and Assessment of the Effects of its Chemical Modifications in vivo
S. Wada, S. Obika*, M. Shibata, T. Yamamoto, M. Nakatani, T. Yamaoka, H. Torigoe, M. Shiba*
Molecular Therapy-Nucleic Acids, 2012, 1, e45.

Synthesis and Evaluation of Novel Caged DNA Alkylating Agents Bearing 3,4-Epoxypiperidine Structure
Y. Kawada, T. Kodama, K. Miyashita, T. Imanishi, S. Obika
Org. Biomol. Chem., 2012, 10, 5102-5108.

Hybridizing Ability and Nuclease Resistance Profile of Backbone Modified Cationic Phosphorothioate Oligonucleotides
S. M. A. Rahman, T. Baba, T. Kodama, M. A. Islam, S. Obika
Bioorg. Med. Chem., 2012, 20, 4098-4102.

Cholesterol-lowering Action of BNA-based Antisense Oligonucleotides Targeting PCSK9 in Atherogenic Diet-induced Hypercholesterolemic Mice
T. Yamamoto, M. Harada-Shiba*, M. Nakatani, S. Wada, H. Yasuhara, K. Narukawa, K. Sasaki, M. Shibata, H. Torigoe, T. Yamaoka, T. Imanishi, S. Obika*
Molecular Therapy-Nucleic Acids, 2012, 1, e22.

Chemical Modification of Triplex-forming Oligonucleotide to Promote Pyrimidine Motif Triplex Formation at Physiological pH
H. Torigoe, O. Nakagawa, T. Imanishi, S. Obika, K. Sasaki
Biochimie, 2012, 94, 1032–1040.
■総説
Towards the Sequence-Selective Recognition of Double-Stranded DNA Containing Pyrimidine-Purine Interruptions by Triplex-Forming Oligonucleotides
Y. Hari, S. Obika, T. Imanishi
Eur. J. Org. Chem., 2012, 2875-2887.

医薬・診断薬への応用に向けた化学修飾核酸アプタマーの開発
桑原 正靖、小比賀 聡
化学工業, 2012, 63, 42-48.

糖部架橋型核酸の医薬への応用
小比賀 聡
医薬ジャーナル, 2012, 48, 65-69.
2011
■論文
Cleavage of Oligonucleotides Containing a P3’N5’ Phosphoramidate Linkage Mediated by Single-stranded Oligonucleotide Templates
K. R. Ito, T. Kodama, F. Makimura, N. Hosoki, T. Osaki, A. Orita, T. Imanishi, S. Obika
Molecules, 2011, 16, 10695-10708.
Design, Synthesis and Properties of Boat-shaped Glucopyranosyl Nucleic Acid
K. Mori, T. Kodama*, S. Obika*
Org. Lett., 2011, 13, 6050-6053.

Synthesis and Properties of a Bridged Nucleic Acid with a Perhydro-1,2-oxazin-3-one Ring
A. R. Shrestha, Y. Hari, A. Yahara, T. Osawa, S. Obika
J. Org. Chem., 2011, 76, 9891-9899.

Increased Expression of Periostin in Vitreous and Fibrovascular Membranes Obtained from Patients with Proliferative Diabetic Retinopathy
S. Yoshida, K. Ishikawa, R. Asato, M. Arima, Y. Sassa, A. Yoshida, H. Yoshikawa, K. Narukawa, S. Obika, J. Ono, S. Ohta, K. Izuhara, T. Kono, T. Ishibashi
Invest. Opthamol. Vis. Sci., 2011, 52, 5670—5678.

Benzylidene Acetal-Type Bridged Nucleic Acids: Changes in Properties Upon Cleavage of the Bridge Triggered by External Stimuli
K. Morihiro, T. Kodama, S. Obika
Chem. Eur. J., 2011, 17, 7918—7926.

Bridged Nucleic Acid Conjugates at 6’-Thiol: Synthesis, Hybridization Properties and Nuclease Resistances
K. Mori, T. Kodama, T. Baba, S. Obika
Org. Biomol. Chem., 2011, 9, 5272—5279.

A 4-[(3R,4R)-dihydroxypyrrolidino]pyrimidin-2-one Nucleobase for a CG Base Pair in Triplex DNA
Y. Hari, M. Akabane, Y. Hatanaka, M. Nakahara, S. Obika
Chem. Commun., 2011, 47, 4424—4426.

Synthesis and Triplex-Forming Ability of Oligonucleotides Bearing 1-Substituted 1H-1,2,3-Triazole Nucleobases
Y. Hari, M. Nakahara, J. Pang, M. Akabane, T. Kuboyama and S. Obika
Bioorg. Med. Chem., 2011, 19, 1162—1166.

2’-O,4’-C-Aminomethylene Bridged Nucleic Acid Modification with Enhancement of Nuclease Resistance Promotes Pyrimidine Motif Triplex Nucleic Acid Formation at Physiological pH
H. Torigoe, S. M. A. Rahman, H. Takuma, N. Sato, T. Imanishi, S. Obika and K. Sasaki
Chem. Eur. J., 2011, 17, 2742—2751.

Interrupted 2’-O,4’-C-Aminomethylene Bridged Nucleic Acid Modification Enhances Pyrimidine Motif Triplex-Forming Ability and Nuclease Resistance Under Physiological Condition
H. Torigoe, S. M. A. Rahman, H. Takuma, N. Sato, T. Imanishi, S. Obika and K. Sasaki
Nucleosides Nucleotides Nucleic Acids, 2011, 30, 63—81.

Stoichiometry-Focused 18F-Labeling of Alkyne-Substituted Oligodeoxynucleotides Using Azido([18F]fluoromethyl)benzenes by Cu-Catalyzed Huisgen Reaction
T. Kuboyama, M. Nakahara, M. Yoshino, Y. Cui, T. Sako, Y. Wada, T. Imanishi, S. Obika*, Y. Watanabe, M*. Suzuki*, H. Doi
Bioorg. Med. Chem., 2011, 19, 249—255.
■総説
Antisense Drug Discovery and Development
T. Yamamoto, K. Narukawa, M. Nakatani and S. Obika
Future Medicinal Chemistry, 2011, 3, 339—365.
■著書
BNA(LNA)の開発とその応用
小比賀 聡, 今西 武
核酸化学のニュートレンド,日本化学会(編), pp181—187, 化学同人 (2011).

2’-O,4’-C-Methyleneoxymethylene Bridged Nucleic Acid (2’,4’-BNACOC)
Y. Hari, T. Kodama, T. Imanishi, S. Obika
"Therapeutic Oligonucleotides: Methods and Protocols," John Goodchild Ed., pp 31—57, Humana Press (2011).
2010
■論文
Study on Suitability of KOD DNA Polymerase for Enzymatic Productions of Artificial Nucleic Acids using Base/Sugar Modified Nucleoside Triphosphates
Y. Takano, M. Kuwahara, Y. Kasahara, H. Nara, H. Ozaki, H. Sawai, A. Sugiyama, S. Obika
Molecules, 2010, 15, 8229–8240.
A Novel Bridged Nucleoside Bearing a Conformationally Switchable Sugar Moiety in Response to Redox Changes
T. Baba, T. Kodama, K. Mori, T. Imanishi, S. Obika
Chem. Commun., 2010, 46, 8058—8060.

Synarticles and DNA Cleavage Evaluation of Epoxypiperidine Derivatives Bearing a Dehydroamino Acid Unit
T. Yamaguchi, Y. Kawada, S. Obika, T. Imanishi, K. Miyashita
Tetrahedron, 2010, 66, 8181—8188.

Double-stranded DNA-templated Cleavage of Oligonucleotides Containing a P3’→N5’ Linkage Triggered by Triplex Formation: The Effects of Chemical Modifications and Remarkable Enhancement in Reactivity
K. R. Ito, T. Kodama, M. Tomizu, Y. Negoro, A. Orita, T. Osaki, N. Hosoki, T. Tanaka, T. Imanishi, S. Obika
Nucleic Acids Res., 2010, 38, 7332−7342.

2’,4’-BNA Bearing a 2-Pyridine Nucleobase for CG Base Pair Recognition in the Parallel Motif Triplex DNA
Y. Hari, S. Matsugu, H. Inohara, Y. Hatanaka, M. Akabane, T. Imanishi, S. Obika
Org. Biomol. Chem., 2010, 8, 4176—4180.

Synthesis, RNA Selective Hybridization and High Nuclease Resistance of an Oligonucleotide Containing Novel Bridged Nucleic Acid With Cyclic Urea Structure
M. Nishida, T. Baba, T. Kodama, A. Yahara, T. Imanishi, S. Obika
Chem. Commun., 2010, 46, 5283—5285.

RNA Interference with 2’,4’-Bridged Nucleic Acid Analogues
S. M. A. Rahman, H. Sato, N. Tsuda, S. Haitani, K. Narukawa, T. Imanishi, S. Obika
Bioorg. Med. Chem., 2010, 18, 3474–3480.
Effect of 3’-End Capping of Aptamer with Various 2’,4’-Bridged Nucleotides: Enzymatic Post-Modification toward a Practical Use of Polyclonal Aptamers
Y. Kasahara, S. Kitadume, K. Morihiro, M. Kuwahara, H. Ozaki, H. Sawai, T. Imanishi, S. Obika
Bioorg. Med. Chem. Lett., 2010, 20, 1626—1629.

Synthesis and Evaluation of Novel 3,4-Epoxypiperidines as Efficient DNA Alkylating Agents
Y. Kawada, T. Kodama, K. Miyashita, T. Imanishi, S. Obika
Heterocycles, 2010, 80, 1249—1265.
■総説
架橋型人工核酸BNAの開発(4):外部刺激応答型人工核酸スイッチへの展開
兒玉 哲也、今西 武、小比賀 聡
Antisense, 2010, 14, 35–44.

架橋型人工核酸BNAの開発(3):三重鎖形成を基盤としたDNA分析法
伊藤 浩介、今西 武、小比賀 聡
Antisense, 2010, 14, 5-15.

オリゴ核酸PET分子プローブの合成法
窪山 剛之、小比賀 聡
創薬研究への分子イメージング応用(遺伝子医学MOOK18)メディカルドゥ, 2010, 60-65.

Bridged Nucleic Acids: Development, Synthesis and Properties
S. Obika, S. M. A. Rahman, A. Fujisaka, Y. Kawada, T. Baba and T. Imanishi
Heterocycles, 2010, 81, 1347-1392.
2009
■論文
Synthesis of Light-Responsive Bridged Nucleic Acid and Changes in Affinity with Complementary ssRNA
K. Morihiro, T. Kodama, M. Nishida, T. Imanishi, S. Obika
ChemBioChem, 2009, 10, 1784—1788.
Smart Conferring of Nuclease Resistance to DNA by 3'-End Protection Using 2',4'-Bridged Nucleoside-5'-Triphosphates
M. Kuwahara, S. Obika, H. Takeshima, Y. Hagiwara, J. Nagashima, H. Ozaki, H. Sawai, T. Imanishi
Bioorg. Med. Chem. Lett., 2009, 19, 2941—2943.

Synthesis and Base-pairing Properties of C-Nucleotides Having 1-Substituted 1H-1,2,3-Triazoles
M. Nakahara, T. Kuboyama, A. Izawa, Y. Hari, T. Imanishi, S. Obika
Bioorg. Med. Chem. Lett., 2009, 19, 3316—3319.

Synergistic Stabilization of Nucleic Acid Assembly by 2’-O,4’-C-Methylene Bridged Nucleic Acid Modification and Additions of Comb-type Cationic Copolymers
H. Torigoe, A. Maruyama, S. Obika, T. Imanishi, T. Katayama
Biochemistry, 2009, 48, 3545—3553.

Design, Synthesis and Evaluation of a Novel Bridged Nucleic Acid, 2’,5’-BNAON, with S-type Sugar Conformation Fixed by an N-O Linkage
T. Kodama, C. Matsuo, H. Ori, T. Miyoshi, S. Obika, K. Miyashita and T. Imanishi
Tetrahedron, 2009, 65, 2116—2123.

A Bridged Nucleic Acid, 2’,4’-BNACOC: Synthesis of Fully Modified Oligonucleotides Bearing Thymine, 5-Methylcytosine, Adenine and Guanine 2’,4’-BNACOC Monomers, and RNA-selective Nucleic Acid Recognition
Y. Mitsuoka, T. Kodama, R. Ohnishi, Y. Hari, T. Imanishi and S. Obika
Nucleic Acids Res., 2009, 37, 1225—1238.

Synthesis of a Novel trans-3’,4’-BNA Monomer Bearing a 4,8-Dioxa-5-azabicyclo[5.3.0]decane Skeleton
T. Kodama, K. Sugaya, T. Baba, T. Imanishi and S. Obika
Heterocycles, 2009, 79, 873—882.

Synthesis and Properties of 2’-Deoxy-trans-3’,4’-BNA with S-Type Sugar Puckering
T. Kodama, K. Sugaya, Y. Harada, Y. Mitsuoka, T. Imanishi and S. Obika
Heterocycles, 2009, 77, 1209—1217.

Synthesis and Properties of a Novel 2’,4’-BNA Bearing a Urea Bridged Structure
A. Yahara, M. Nishida, T. Baba, T. Kodama, T. Imanishi, S. Obika
Nucleic Acids Symp. Ser., 2009, 53, 11—12.

Synthesis and Properties of a Novel Artificial Nucleoside That Acts as a Redox Switch
T. Baba, T. Kodama, T. Imanishi, S. Obika
Nucleic Acids Symp. Ser., 2009, 53, 107—108.

Promotion of Triplex Formation by 3’-Amino-2’-O,4’-C-methylene Bridged Nucleic Acid Modification
K. Sasaki, S. M. A. Rahman, N. Sato, S. Obika, T. Imanishi, H. Torigoe
Nucleic Acids Symp. Ser., 2009, 53, 159—160.

Development of Light-responsive BNA toward the Spatiotemporal Control of Gene Expression
K. Morihiro, T. Kodama, M. Nishida, T. Imanishi, S. Obika
Nucleic Acids Symp. Ser., 2009, 53, 187—188.
■総説
架橋型人工核酸BNAの開発(2):アンチセンス法への応用
小比賀 聡、今西 武
Antisense, 2009, 13, 19-29.

架橋型人工核酸BNAの開発(1):分子設計と合成
小比賀 聡、今西 武
Antisense, 2009, 13, 3-12.

Synarticles of Several Types of Bridged Nucleic Acids
S. M. A. Rahman, T. Imanishi and S. Obika
Chem. Lett., 2009, 38, 512—517 (Highlight Review).
■著書
ブリッジ型人工核酸によるHCV-IRES領域標的アンチセンス核酸の開発
小比賀 聡, 今西 武
バイオ医薬の開発技術とシーズ, 山本重夫 (監), pp235—245, シーエムシー出版 (2009).

糖部架橋型核酸医薬の合成とその性質
小比賀 聡, 今西 武
核酸医薬の最前線, 和田 猛 (監), pp55—66, シーエムシー出版 (2009).
2008
■論文
Synthesis and Properties of 3’-Amino-2’,4’-BNA, A Bridged Nucleic Acid with a N3’P5’ Phosphoramidate Linkage
S. Obika, S. M. A. Rahman, B. Song, M. Onoda, M. Koizumi, K. Morita and T. Imanishi
Bioorg. Med. Chem., 2008, 16, 9230—9237.
Systematic Analysis of Enzymatic DNA Polymerization Using Oligo-DNA Templates and Triphosphate Analogs Involving 2’,4’-Bridged Nucleosides
M. Kuwahara, S. Obika, J. Nagashima, Y. Ohta, Y. Suto, H. Ozaki, H. Sawai and T. Imanishi
Nucleic Acids Res., 2008, 36, 4257—4265.

Design, Synthesis and Properties of 2’,4’-BNANC: A Bridged Nucleic Acid Analogue
S. M. A. Rahman, S. Seki, S. Obika, H. Yoshikawa, K. Miyashita and T. Imanishi
J. Am. Chem. Soc., 2008, 130, 4886—4896.

Recognition of T·A Interruption by 2’,4’-BNAs Bearing Heteroaromatic Nucleobases Through Parallel Motif Triplex Formation
S. Obika, H. Inohara, Y. Hari and T. Imanishi
Bioorg. Med. Chem., 2008, 16, 2945—2954.

Design and Chemical Synthesis of a 2',4'-BNA Probe for 7,8-Dihydro-8-oxoguanine-containing Double Stranded DNA
T. Miyoshi, T. Kodama, S. Obika, T. Imanishi
Nucleic Acids Symp. Ser., 2008, 52, 305—306.

Promotion of Triplex Formation by 2'-O,4'-C-Aminomethylene Bridged Nucleic Acid (2',4'-BNANC) Modification
K. Sasaki, S. M. A. Rahman, S. Obika, T. Imanishi, H. Torigoe
Nucleic Acids Symp. Ser., 2008, 52, 419—420.

Biologically active 2-5A analogs containing 3'-O,4'-C-propylene adenosine as potent RNase L agonists
K. Morita, S. Obika, T. Imanishi, Y. Kitade, M. Koizumi
Nucleic Acids Symp. Ser., 2008, 52, 637—638.

Promotion of Acid-Mediated P-N Bond Cleavage of 5’-Amino-2’,4’-BNA Oligonucleotides by Triplex Formation: Effects of Neighboring Residues
S. Obika, M. Tomizu, Y. Negoro, A. Orita, T. Imanishi
Collection Symp. Ser., 2008, 10, 423—425.
2007
■論文
Double-stranded DNA-templated Oligonucleotide Digestion Triggered by Triplex Formation
S. Obika, M. Tomizu, Y. Negoro, A. Orita, O. Nakagawa and T. Imanishi
ChemBioChem, 2007, 8, 1924—1928.
Biologically Stable 2-5A Analogues Containing 3’-O,4’-C-Bridged Adenosine as Potent RNase L Agonists
K. Morita, M. Kaneko, S. Obika, T. Imanishi, Y. Kitade and M. Koizumi
ChemMedChem, 2007, 2, 1703—1707.

N-Methyl Substituted 2’,4’-BNANC: A Highly Nuclease-resistant Nucleic Acid Analogue with High-affinity RNA Selective Hybridization
K. Miyashita, S. M. A. Rahman, S. Seki, S. Obika and T. Imanishi
Chem. Commun., 2007, 3765—3767.

Development of a Novel Nucleoside Analogue with S-type Sugar Conformation: 2'-Deoxy-trans-3',4'-Bridged Nucleic Acids
T. Osaki, S. Obika, Y. Harada, Y. Mitsuoka, K. Sugaya, M. Sekiguchi and T. Imanishi
Tetrahedron, 2007, 63, 8977—8986.

Acid-mediated Cleavage of Oligonucleotide P3’N5’ Phosphoramidates Triggered by Sequence-specific Triplex Formation
S. Obika, M. Tomizu, Y. Negoro, T. Osaki, A. Orita, Y. Ueyama, O. Nakagawa and T. Imanishi
Nucleosides Nucleotides Nucleic Acids, 2007, 26, 893—896.

2’,4’-BNANC: A Novel Bridged Nucleic Acid Analogue with Excellent Hybridizing and Nuclease Resistance Profiles
S. M. A. Rahman, S. Seki, K. Utsuki, S. Obika, K. Miyashita and T. Imanishi
Nucleosides Nucleotides Nucleic Acids, 2007, 26, 1625—1628.

Synthesis of Novel 2’-Deoxy Type trans-3’,4’-Bridged Nucleic Acid
T. Osaki, S. Obika, Y. Harada, Y. Mitsuoka, K. Sugaya, M. Sekiguchi, R. Somjing and T. Imanishi
Nucleosides Nucleotides Nucleic Acids, 2007, 26, 1079—1082.

Highly Stable Pyrimidine-motif Triplex Formation at Physiological pH Values by a Bridged Nucleic Acid Analogue
S. M. A. Rahman, S. Seki, S. Obika, K. Miyashita and T. Imanishi
Angew. Chem. Int. Ed., 2007, 46, 4306—4309; Angew. Chem., 2007, 119, 4384—4387.

Polymerisation of a DNA Strand Using Oligo-DNA Template with Modified Bases, Sugars and Phosphates
J. Nagashima, S. Minezaki, S. Obika, T. Imanishi, M. Kuwahara and H. Sawai
Nucleic Acids Symp. Ser., 2007, 51, 55—56.

Inhibition of bcl-xL Expression by Antisense Oligonucleotides Containing Various Bridged Nucleic Acids (BNAs)
S. Roongjang, K. Takahashi, S. Obika and T. Imanishi
Nucleic Acids Symp. Ser., 2007, 51, 113—114.

Synthesis and Properties of a 2'-Deoxy Analogue of trans-3',4'-BNA with an S-type Sugar Conformation
K. Sugaya, Y. Harada, Y. Mitsuoka, T. Osaki, S. Obika, T. Kodama and T. Imanishi
Nucleic Acids Symp. Ser., 2007, 51, 155—156.

Synthesis and Chemical Properties of a Novel 2',4'-Bridged Nucleic Acid Analogue with a Seven-membered Cyclic Carbamate Structure
M. Nishida, T. Kodama, S. Obika and T. Imanishi
Nucleic Acids Symp. Ser., 2007, 51, 157—158.

Synthesis and Evaluation of a Novel 2',5'-Bridged Nucleic Acid with Sugar Conformation Fixed to S-type by N-O Linkage
T. Kodama, C. Matsuo, H. Ori, S. Obika, K. Miyashita and T. Imanishi
Nucleic Acids Symp. Ser., 2007, 51, 159—160.

Antisense Activity of 2',4'-BNA Targeted to PPAR Gamma in THP-1 and HCT116 Cells
K. Tachibana, T. Katayama, C. Ueda, M. Sumitomo, M. Tagami, K. Ishimoto, D. Yamasaki, T. Tanaka, T. Hamakubo, J. Sakai, T. Kodama, S. Obika, T. Imanishi and T. Doi
Nucleic Acids Symp. Ser., 2007, 51, 441—442.

核酸医薬:テーラーメード医療に向けた新たな創薬
小比賀 聡
薬事日報, 2007年7月9日号
2006
■論文
Synthesis and Properties of trans-3',4'-Bridged Nucleic Acids Having Typical S-type Sugar Conformation
M. Sekiguchi, S. Obika, Y. Harada, T. Osaki, R. Somjing, Y. Mitsuoka, N. Shibata, M. Masaki and T. Imanishi
J. Org. Chem., 2006, 71, 1306—1316.
Synthesis and Properties of 2'-O,4'-C-Methyleneoxymethylene Bridged Nucleic Acid
Y. Hari, S. Obika, R. Ohnishi, K. Eguchi, T. Osaki, H. Ohishi and T. Imanishi
Bioorg. Med. Chem., 2006, 14, 1029—1038.

Synthesis of 2’,4’-BNACOC Bearing a Purine Nucleobase
Y. Mitsuoka, R. Ohnishi, Y. Hari, S. Obika and T. Imanishi
Nucleic Acids Symp. Ser., 2006, 50, 13—14.

High-affinity RNA Mimicking Binding of 2’,4’-BNANC Towards Complementary Strands: A Comparative Study with 2’,4’-BNA/LNA
S. M. A. Rahman, S. Seki, K. Utsuki, S. Obika, K. Miyashita and T. Imanishi
Nucleic Acids Symp. Ser., 2006, 50, 195—196.

Antisense Activity of 2’,4’-BNA Targetd to bcl-xL Gene in HepG2 Cell
S. Roongjang, K. Takahashi, M. Park, S. Obika and T. Imanishi
Nucleic Acids Symp. Ser., 2006, 50, 289—290.
■総説
ゲノム創薬の高機能性基盤素材としての新しいブリッジ型人工核酸BNA
今西 武、小比賀 聡
化学工業, 2006, 57, 192—197.
2005
■論文
Promotion of Stable Triplex Formation by Partial Incorporation of 2',5'-Phosphodiester Linkages into Triplex-forming Oligonucleotides S. Obika, A. Hiroto, O. Nakagawa and T. Imanishi Chem. Commun., 2005, 2793—2795.
Synthesis and Triplex-forming Ability of 2',4'-BNAs Bearing Imidazoles as a Nucleobase
Y. Hari, S. Obika, H. Inohara, M. Ikejiri, D. Une and T. Imanishi
Chem. Pharm. Bull., 2005, 53, 843—846.

Presence of 2',5'-Linkages in a Homopyrimidine DNA Oligonucleotide Promotes Stable Triplex Formation under Physiological Conditions
S. Obika, A. Hiroto, O. Nakagawa and T. Imanishi
Nucleosides Nucleotides Nucleic Acids, 2005, 24, 1055—1058.

Synthesis and Properties of a Novel Bridged Nucleic Acid Analogue, 5'-Amino-3',5'-BNA
M. Sekiguchi, S. Obika, R. Somjing and T. Imanishi
Nucleosides Nucleotides Nucleic Acids, 2005, 24, 1097—1100.

Combination of Poly(L-lysine)-graft-dextran Copolymer and 2'-O,4'-C-Methylene Bridged Nucleic Acid (2',4'-BNA) Modification Synergistically Stabilizes Pyrimidine Motif Triplex at Neutral pH
H. Torigoe, T. Katayama, S. Obika, A. Maruyama and T. Imanishi
Nucleosides Nucleotides Nucleic Acids, 2005, 24, 635—638.

Adjustment of the g Dihedral Angle of an Oligonucleotide P3'N5' Phosphoramidate Enhances Its Binding Affinity towards Complementary Strands
S. Obika, M. Sekiguchi, R. Somjing and T. Imanishi
Angew. Chem. Int. Ed., 2005, 44, 1944—1947; Angew. Chem., 2005, 117, 1980—1983.

Synthesis and Properties of 2',4'-BNANC, A Second Generation BNA
S. M. A. Rahman, S. Seki, K. Utsuki, S. Obika, K. Miyashita and T. Imanishi
Nucleic Acids Symp. Ser., 2005, 49, 5—6.

Promotion of Acid-mediated Cleavage of Oligonucleotide P3'->N5' Phosphoramidates by Triplex Formation: A Novel Approach to Sequence-Specific DNA Detection
M. Tomizu, O. Nakagawa, S. Obika and T. Imanishi
Nucleic Acids Symp. Ser., 2005, 49, 157—158.

Synthesis and Triplex-forming Properties of 2',4'-BNA Derivatives Bearing Pyridines as An Unnatural Nucleobase
S. Matsugu, H. Inohara, S. Obika and T. Imanishi
Nucleic Acids Symp. Ser., 2005, 49, 159—160.

Effects of the 2',4'-BNA Modification on the Sequence Specificity of Molecular Beacons
S. Fujii, S. Obika and T. Imanishi
Nucleic Acids Symp. Ser., 2005, 49, 211—212.

Antigene-block Strategy: Effective Regulation of Gene Expression by 2',4'-BNA-modified TFOs with An Additional Stem-Loop Structure
N. Tsuda, A. Matsumoto, A. Ito, T. Uneda, A. Tanabe, S. Obika and T. Imanishi
Nucleic Acids Symp. Ser., 2005, 49, 335—336.
■総説
高機能化siRNAによる遺伝子発現制御 –BNAによるsiRNAの機能化-
津田直人、小比賀 聡、今西 武
バイオテクノロジージャーナル, 2005, 5, 738—742.

新規RNA型人工核酸
今西 武、小比賀 聡
臨床化学, 2005, 34, 224—232.
■著書
Sugar-Modified Nucleic Acid Analogues as Potential Materials for Genomic Technologies
T. Imanishi and S. Obika
"Frontiers in Organic Chemistry," Atta-ur-Rahman Ed., pp 209—228, Bentham Science Publishers (2005).

Effect of Modifications on the Intracellular Activity of a DNA Enzyme
M. Warashina, B. Nawrot, S. Obika, L. A. Woniak, T. Kuwabara, T. Imanishi, W. J. Stec and K. Taira
“Synthetic Nucleic Acids as Inhibitors of Gene Expression,” L. M. Khachigian Ed., pp 95—113, CRC Press, Boca Raton (2005).

BNA(LNA)オリゴを用いるアンチセンス法
今西 武, 小比賀 聡
RNAiとアンチセンス法, 関根 光雄, 多比良 和誠 (編), pp199—210, 講談社サイエンティフィク (2005).
2004
■論文
Synthesis and Conformation of a Novel Bridged Nucleic Acid Having a trans-Fused 3,5,8-Trioxabicyclo[5.3.0]decane Structure
S. Obika, T. Osaki, M. Sekiguchi, R. Somjing, Y. Harada and T. Imanishi
Tetrahedron Lett., 2004, 45, 4801—4804.
Synthesis and Properties of a Novel Bridged Nucleic Acid Analogue Bearing a P3'->N5' Phosphoramidate Linkage, 5'-Amino-3',5'-BNA
M. Sekiguchi, S. Obika, R. Somjing and T. Imanishi
Nucleic Acids Symp. Ser., 2004, 48, 7—8.

2',4'-BNA Derivatives Bearing an Unnatural Nucleobase: Synthesis and Application to Triplex-forming Oligonucleotides
H. Inohara, S. Obika and T. Imanishi
Nucleic Acids Symp. Ser., 2004, 48, 63—64.

Synergistic Stabilization of Triplex by Combination of Comb-type Cationic Copolymer and 2',4'-BNA
T. Katayama, A. Maruyama, S. Obika, T. Imanishi and H. Torigoe
Nucleic Acids Symp. Ser., 2004, 48, 165—166.

「アンチセンス・アンチジーン」特集によせて
小比賀 聡
生物工学会誌, 2004, 82, 135–135.
■総説
ゲノムテクノロジー基盤素材としての架橋型人工核酸BNA
(日本薬学会奨励賞受賞記念総説)
小比賀 聡
薬学雑誌, 2004, 124, 781—790.

Development of Bridged Nucleic Acid Analogues for Antigene Technology
(日本薬学会奨励賞受賞記念総説)
S. Obika
Chem. Pharm. Bull., 2004, 52, 1399—1404.

架橋型人工核酸 BNA の開発とそのアンチセンス・アンチジーン特性
小比賀 聡
生物工学会誌, 2004, 82, 149–151.
2003
■論文
Conformations and Dynamics of Ets-1 ETS Domain-DNA Complexes
S. Y. Reddy, S. Obika and T. C. Bruice
Proc. Natl. Acad. Sci. USA, 2003, 100, 15475—15480.
Sequence Specific DNA Binding of Ets-1 Transcription Factor: Molecular Dynamics Study on the Ets Domain-DNA Complexes
S. Obika, S. Y. Reddy and T. C. Bruice
J. Mol. Biol., 2003, 331, 345—359.

Triplex Formation Involving 2'-O,4'-C-Methylene Bridged Nucleic Acid (2',4'-BNA) with 1-Isoquinolone Base Analogue: Efficient and Selective Recognition of C : G Interruption
H. Torigoe, Y. Hari, S. Obika and T. Imanishi
Nucleosides Nucleotides Nucleic Acids, 2003, 22, 1571—1573.

Triplex Formation Involving 2'-O,4'-C-Methylene Bridged Nucleic Acid (2',4'-BNA) with 2-Pyridone Base Analogue: Efficient and Selective Recognition of C : G Interruption
H. Torigoe, Y. Hari, S. Obika and T. Imanishi
Nucleosides Nucleotides Nucleic Acids, 2003, 22, 1097—1099.

Synthesis of a Novel Bridged Nucleoside Bearing a Fused-azetidine Ring, 3'-Amino-3',4'-BNA Monomer
S. Obika, J. Andoh, M. Onoda, O. Nakagawa, A. Hiroto, T. Sugimoto and T. Imanishi
Tetrahedron Lett., 2003, 44, 5267—5270.

Synthesis and Properties of a Novel Bridged Nucleic Acid with a P3'N5' Phosphoramidate Linkage, 5'-Amino-2',4'-BNA
S. Obika, O. Nakagawa, A. Hiroto, Y. Hari and T. Imanishi
Chem. Commun., 2003, 2202—2203.

Selective Recognition of CG Interruption by 2',4'-BNA Having 1-Isoquinolone as a Nucleobase in a Pyrimidine Motif Triplex Formation
Y. Hari, S. Obika, M. Sekiguchi and T. Imanishi
Tetrahedron, 2003, 59, 5123—5128.

Triplex Formation with 2'-O,4'-C-Ethylene-bridged Nucleic Acids (ENA) Having C3'-endo Conformation at Physiological pH
M. Koizumi, K. Morita, M. Daigo, S. Tsutumi, K. Abe, S. Obika and T. Imanishi
Nucleic Acids Res., 2003, 31, 3267—3273.

The Unique Target Specificity of a Nonpeptide Chemokine Receptor Antagonist: Selective Blockade of Two Th1 Chemokine Receptors CCR5 and CXCR3
P. Gao, X. Y. Zhou, Y. Yashiro-Ohtani, Y. F. Yang, N. Sugimoto, S. Ono, T. Nakanishi, S. Obika, T. Imanishi, T. Egawa, T. Nagasawa, H. Fujiwara and T. Hamaoka
J. Leukoc. Biol., 2003, 73, 273—280.

A Novel Nucleic Acid Analogue, 3'-Amino-2'-deoxy-3',4'-BNA, with an N3'->P5' Phosphoramidate Linkage and an S-type Conformation
O. Nakagawa, A. Hiroto, S. Obika and T. Imanishi
Nucleic Acids Res. Suppl, 2003, 3, 87—88.

trans-3',4'-BNAs, Novel Nucleic Acid Analogues with an S-type Conformation: Synthesis and Incorporation into Oligonucleotides
M. Sekiguchi, T. Osaki, Y. Harada, S. Obika and T. Imanishi
Nucleic Acids Res. Suppl, 2003, 3, 111—112.
2002
■論文
A Non-peptide CCR5 Antagonist Inhibits Collagen-induced Arthritis by Modulating T Cell Migration without Affecting Anti-collagen T Cell Responses
Y.-F. Yang, T. Mukai, Y. Uekusa, P. Gao, N. Yamaguchi, S. Ono, H. Iwaki, S. Obika, T. Imanishi, T. Tsujimura, T. Hamaoka and H. Fujiwara
Eur. J. Immunol., 2002, 32, 2124—2132.
A Pivotal Role for CC Chemokine Receptor 5 in T-cell Migration to Tumor Sites Induced by Interleukin 12 Treatment in Tumor-hearing Mice
Y. Uekusa, W.-G. Yu, T. Mukai, P. Gao, N. Yamaguchi, M. Murai, K. Matsushima, S. Obika, T. Imanishi, Y. Higashibata, S. Nomura, Y. Kitamura, H. Fujiwara and T. Hamaoka
Cancer Res., 2002, 62, 3751—3758.

Stable Oligonucleotide-directed Triplex Formation at Target Sites with CG Interruptions: Strong Sequence-specific Recognition by 2',4'-Bridged Nucleic Acid Containing 2-Pyridones under Physiological Conditions
S. Obika, Y. Hari, M. Sekiguchi and T. Imanishi
Chem. Eur. J., 2002, 8, 4796—4802.

Synthesis and Conformation of a Novel Bridged Nucleoside with S-type Sugar Puckering, trans-3',4'-BNA Monomer
S. Obika, M. Sekiguchi, T. Osaki, N. Shibata, M. Masaki, Y. Hari and T. Imanishi
Tetrahedron Lett., 2002, 43, 4365—4368.

Synthesis and Conformation of 3',4'-BNA Monomers, 3'-O,4'-C-Methyleneribonucleosides
S. Obika, K. Morio, D. Nanbu, Y. Hari, H. Itoh and T. Imanishi
Tetrahedron, 2002, 58, 3039—3049.

A 3,4-Epoxypiperidine Structure as a Novel and Simple DNA-Cleavage Unit
K. Miyashita, M. Park, S. Adachi, S. Seki, S. Obika and T. Imanishi
Bioorg. Med. Chem. Lett., 2002, 12, 1075—1077.

Effective Synthesis of C-Nucleosides with 2',4'-BNA Modification
Y. Hari, S. Obika, M. Sakaki, K. Morio, Y. Yamagata and T. Imanishi
Tetrahedron, 2002, 58, 3051—3063.

Synthesis and Properties of 5'-Amino-2',4'-BNA Modified Oligonucleotides with P3'->N5' Phosphoramidate Linkages
S. Obika, O. Nakagawa, A. Hiroto, Y. Hari and T. Imanishi
Nucleic Acids Res. Suppl, 2002, 2, 25—26.

Binding of Threading Intercalator to Nucleic Acids: Thermodynamic Analyses
H. Torigoe, S. Sato, K. Yamashita, S. Obika, T. Imanishi and S. Takenaka
Nucleic Acids Res. Suppl, 2002, 2, 55—56.<

Synthesis and Properties of Oligonucleotides Containing Novel 2',4'-BNA Analogues (2',4'-BNACOC)
Y. Hari, T. Osaki, K. Eguchi, S. Obika and T. Imanishi
Nucleic Acids Res. Suppl, 2002, 2, 147—148.

Triplex Formation Involving 2',4'-BNA with Isoquinolone Base Analogue: Efficient and Selective Recognition of C:G Interruption
H. Torigoe, Y. Hari, S. Obika and T. Imanishi
Nucleic Acids Res. Suppl, 2002, 2, 183—184.
■総説
BNAs: Novel Nucleic Acid Analogs with a Bridged Sugar Moiety
T. Imanishi and S. Obika
Chem. Commun., 2002, 1653—1659. (Feature Article)

アンチセンスBNAオリゴヌクレオチドを用いた遺伝子発現抑制
今西 武, 小比賀 聡
日薬理誌, 2002, 120, 85—90.
2001
■論文
Promotion of Triplex Formation by 2 '-O,4 '-C-Methylene Bridged Nucleic Acid (2’,4’-BNA) Modification: Thermodynamic and Kinetic Studies
H. Torigoe, S. Obika and T. Imanishi
Nucleosides Nucleotides Nucleic Acids, 2001, 20, 1235—1238.
2'-O,4'-C-Methylene Bridged Nucleic Acid Modification Promotes Pyrimidine Motif Triplex DNA Formation at Physiological pH: Thermodynamic and Kinetic Studies
H. Torigoe, Y. Hari, M. Sekiguchi, S. Obika and T. Imanishi
J. Biol. Chem., 2001, 276, 2354—2360.

3'-Amino-2',4'-BNA: Novel Bridged Nucleic Acids Having an N3'P5' Phosphoramidate Linkage
S. Obika, M. Onoda, K. Morita, J. Andoh, M. Koizumi and T. Imanishi
Chem. Commun., 2001, 1992—1993.

A 2',4'-Bridged Nucleic Acid Containing 2-Pyridone as a Nucleobase: Efficient Recognition of a C•G Interruption by Triplex Formation with a Pyrimidine Motif
S. Obika, Y. Hari, M. Sekiguchi and T. Imanishi
Angew. Chem., Int. Ed., 2001, 40, 2079—2081; Angew. Chem., 2001, 113, 2149—2151.

2'-O,4'-C-Methylene Bridged Nucleic Acid (2',4'-BNA): Synthesis and Triplex-forming Properties
S. Obika, T. Uneda, T. Sugimoto, D. Nanbu, T. Minami, T. Doi and T. Imanishi
Bioorg. Med. Chem., 2001, 9, 1001—1011.

Symmetrical Cationic Triglycerides: An Efficient Synthesis and Application to Gene Transfer
S. Obika, W. Yu, A. Shimoyama, T. Uneda, K. Miyashita, T. Doi and T. Imanishi
Bioorg. Med. Chem., 2001, 9, 245—254.

Inhibition of ICAM-I Gene Expression by Antisense 2',4'-BNA Oligonucleotides
S. Obika, R. Hemamayi, T. Masuda, T. Sugimoto, S. Nakagawa, T. Mayumi and T. Imanishi
Nucleic Acids Res. Suppl, 2001, 1, 145—146.

2',4'-BNA Bearing Unnatural Nucleobases: Toward the Expansion of the Target Sequence of Double-stranded DNA in Triplex Formation
S. Obika, Y. Hari, H. Inohara and T. Imanishi
Nucleic Acids Res. Suppl, 2001, 1, 171—172.

Triplex Formation Involving 2',4'-BNA with 2-Pyridone Base Analogue: Efficient and Selective Recognition of C:G Interruption
H. Torigoe, Y. Hari, S. Obika and T. Imanishi
Nucleic Acids Res. Suppl, 2001, 1, 281—282.
■総説
ポストゲノム時代に向けた新しい遺伝子治療薬の開発研究
—アンチセンス・アンチジーン法の実用化に向けて—
今西 武, 小比賀 聡
生産と技術, 2001, 53, 53—56.

核酸分子の相互作用を光でコントロール!
小比賀 聡
ファルマシア, 2001, 37, 66—67.
2000
■論文
Triplex-forming Enhancement with High Sequence Selectivity by Single 2'-O,4'-C-Methylene Bridged Nucleic Acid (2',4'-BNA) Modification
S. Obika, Y. Hari, T. Sugimoto, M. Sekiguchi and T. Imanishi
Tetrahedron Lett., 2000, 41, 8923—8927.
Synthesis of Conformationally Locked C-Nucleosides Having a 2,5-Dioxabicyclo[2.2.1]heptane Ring System
S. Obika, Y. Hari, K. Morio and T. Imanishi
Tetrahedron Lett., 2000, 41, 215—219.

Triplex Formation by an Oligonucleotide Containing Conformationally Locked C-Nucleoside, 5-(2-O,4-C-Methylene-b-D-ribofuranosyl)oxazole
S. Obika, Y. Hari, K. Morio and T. Imanishi
Tetrahedron Lett., 2000, 41, 221—224.

Synthesis and Triplex Forming Ability of Conformationally Locked Oligonucleotides Containing Unnatural Nucleobases: Efficient Recognition of a C•G Interruption
S. Obika, Y. Hari, M. Sekiguchi and T. Imanishi
Nucleic Acids Symp. Ser., 2000, 44, 131—132.

Promotion of Triplex Formation by a Fixed N-form Sugar Puckering: Thermodynamic and Kinetic Studies
H. Torigoe, S. Obika and T. Imanishi
Nucleic Acids Symp. Ser., 2000, 44, 241—242.
■総説
糖部立体配座を固定した人工ヌクレオシド及びオリゴヌクレオチド類縁体の合成とその特性
(日本薬学会近畿支部奨励賞受賞記念総説)
小比賀 聡
薬学雑誌, 2000, 120, 147—158.
1999
■論文
Gene Transfer Mediated by YKS-220 Cationic Particles: Convenient and Efficient Gene Delivery Reagent
W. Yu, A. Shimoyama, T. Uneda, S. Obika, K. Miyashita, T. Doi and T. Imanishi
J. Biochem., 1999, 125, 1034—1038.
Facile Synthesis and Conformation of 3'-O,4'-C-Methyleneribonucleosides
S. Obika, K. Morio, Y. Hari and T. Imanishi
Chem. Commun., 1999, 2423—2424.

Synthesis of a Conformationally Locked AZT Analogue, 3'-Azido-3'-deoxy-2'-O,4'-C-methylene-5-methyluridine
S. Obika, J. Andoh, T. Sugimoto, K. Miyashita and T. Imanishi
Tetrahedron Lett., 1999, 40, 6465—6468.

Preparation and Properties of 2',5'-Linked Oligonucleotide Analogues Containing 3'-O,4'-C-Methyleneribonucleosides
S. Obika, K. Morio, Y. Hari and T. Imanishi
Bioorg. Med. Chem. Lett., 1999, 9, 515—518.

Properties of Cationic Liposomes Composed of Cationic Lipid YKS-220 Having an Ester Linkage: Adequate Stability, High Transfection Efficiency, and Low Cytotoxicity
S. Obika, W. Yu, A. Shimoyama, T. Uneda, T. Minami, K. Miyashita, T. Doi and T. Imanishi
Biol. Pharm. Bull., 1999, 22, 187—190.
■総説
Syntheses and Properties of Novel Conformationally Restrained Nucleoside Analogues
T. Imanishi and S. Obika
J. Syn. Org. Chem., Jpn., 1999, 57, 969—980.
1998
■論文
Stability and Structural Features of the Duplexes Containing Nucleoside Analogues with a Fixed N-type Conformation, 2'-O,4'-C-Methyleneribonucleosides
S. Obika, D. Nanbu, Y. Hari, J. Andoh, K. Morio, T. Doi and T. Imanishi
Tetrahedron Lett., 1998, 39, 5401—5404.
Studies on Novel and Chiral 1,4-Dihydropyridines. VI. Preparation of a Polymer-supported 1,4-Dihydropyridine Having a Chiral Sulfinyl Ggoup and Its Application to Biomimetic Reduction
S. Obika, T. Nishiyama, S. Tatematsu, M. Nishimoto, K. Miyashita and T. Imanishi
Heterocycles, 1998, 49, 261—267.
1997
■論文
Synthesis of 2'-O,4'-C-Methyleneuridine and -cytidine. Novel Bicyclic Nucleosides Having a Fixed C3'-endo Sugar Puckering
S. Obika, D. Nanbu, Y. Hari, K. Morio, Y. In, T. Ishida and T. Imanishi
Tetrahedron Lett., 1997, 38, 8735—8738.
Synthesis and Conformation of 3'-O,4'-C-Methyreneribonucleosides, Novel Bicyclic Nucleoside Analogs for 2',5'-Linked Oligonucleotide Modification
S. Obika, K. Morio, D. Nanbu and T. Imanishi
Chem. Commun., 1997, 1643—1644.

A Symmetrical and Biodegradable Cationic Lipid. Synthesis and Application for Efficient Gene Transfection
S. Obika, W. Yu, A. Shimoyama, T. Uneda, K. Miyashita, T. Doi and T. Imanishi
Bioorg. Med. Chem. Lett., 1997, 7, 1817—1820.

Studies on Novel and Chiral 1,4-Dihydropyridines. IV. Mechanistic Aspects of the Asymmetric Reduction with Chiral NADH Model Compounds, (SS)-3-(p-Tolylsulfinyl)-1,4-dihydropyridines
S. Obika, T. Nishiyama, S. Tatematsu, K. Miyashita and T. Imanishi
Tetrahedron, 1997, 53, 3073—3082.

Studies on Novel and Chiral 1,4-Dihydropyridines. III. Asymmetric Reduction of Some Ketones with Novel NADH Model Compounds, (SS)-3-(p-Tolylsulfinyl)-1,4-dihydropyridines
S. Obika, T. Nishiyama, S. Tatematsu, K. Miyashita, C. Iwata and T. Imanishi
Tetrahedron, 1997, 53, 593—602.

Syntheses of 1-Substituted (SS)-3-p-Tolylsulfinyl-1,4-dihydropyridines, Chiral NADH Model Compounds
S. Obika, T. Nishiyama, S. Tatematsu, M. Nishimoto, K. Miyashita and T. Imanishi
Heterocycles, 1997, 44, 537—542.

Studies on Novel and Chiral 1,4-Dihydropyridines. V. Hantzsch-type 1,4-Dihydropyridines Having a Chiral Sulfinyl Group: Syntheses, Structures, and Biological Activity as a Calcium Channel Antagonist
K. Miyashita, M. Nishimoto, T. Ishino, H. Murafuji, S. Obika, O. Muraoka and T. Imanishi
Tetrahedron, 1997, 53, 4279—4290.
■総説
DNAとRNAを識別するアンチセンス分子
小比賀 聡
ファルマシア, 1997, 33, 629—629.
1996
■論文
Properties of Novel Oligonucleotide Analogues Containing an Acyclic Nucleoside and a Carbamate Linkage
S. Obika, Y. Takashima, Y. Matsumoto, A. Shimoyama, Y. Koishihara, Y. Ohsugi, T. Doi and T. Imanishi
Bioorg. Med. Chem. Lett., 1996, 6, 1357—1360.
Stereospecific 4-Hydrogen Transfer in the Asymmetric Reduction Using (SS)-3-(p-Tolylsulfinyl)-1,4-dihydropyridines, NADH Model Compounds
S. Obika, T. Nishiyama, S. Tatematsu, K. Miyashita and T. Imanishi
Chem. Lett., 1996, 853—854.

Effect of the Neighboring Oxygenated Substituent on Asymmetric Reduction with Hantzsch-type 1,4-Dihydropyridines Having a Chiral Sulfinyl Group
K. Miyashita, M. Nishimoto, H. Murafuji, A. Murakami, S. Obika, Y. In, T. Ishida and T. Imanishi
Chem. Commun., 1996, 2535—2536.

Novel and Regioselective Lithiation of the Unsymmetrical Hantzsch-type 1,4-Dihydropyridine by Participation of the Neighboring Sulfinyl Group
K. Miyashita, M. Nishimoto, H. Murafuji, S. Obika and T. Imanishi
Chem. Pharm. Bull., 1996, 44, 457—459.

Studies on Novel and Chiral 1,4-Dihydropyridines. 1. Synthesis and Conformational Analysis of Novel NADH Model Compounds, N-Substituted (S)-3-(p-Tolylsulfinyl)-1,4-dihydropyridines
T. Imanishi, S. Obika, T. Nishiyama, M. Nishimoto, Y. Hamano, K. Miyashita and C. Iwata
Chem. Pharm. Bull., 1996, 44, 267—272.
1995
■論文
Syntheses of Novel Nucleoside Dimer Analogues Containing an Acyclic Nucleoside and a Carbamate Linkage
S. Obika, Y. Takashima, Y. Matsumoto, K. Kuromaru and T. Imanishi
Tetrahedron Lett., 1995, 36, 8617—8620.
Novel and Chiral Hantzsch-type 1,4-Dihydropyridines Having a p-Tolylsulfinyl Group. Synthesis and Biological Activities as Calcium Channel Antagonists
K. Miyashita, M. Nishimoto, T. Ishino, S. Obika and T. Imanishi
Chem. Pharm. Bull. 1995, 43, 711—713.

実験化学の視点から見た情報化学
小比賀 聡
CICSJ Bull., 1995, 13, 5—8.
1994
■論文
Transdermal Penetration-Enhancing Effect and Its Mechanism of Novel Triglycerides Having Quaternary Ammonium Group
K. Kubo, N. Tojyo, W. Yu, S. Obika, T. Imanishi and T. Mayumi
Yakubutsu Dotai, 1994, 9, s86—s89.
1992
■論文
Syntheses of Optically Active 1,4-Dihydropyridines Having a p-Tolylsulfinyl Group and Their Applications
T. Imanishi, S. Obika, M. Nishimoto, K. Shikada, K. Miyashita and C. Iwata
J. Pharmacobio-Dyn. 1992, 15, s-39—s-39.
大阪大学大学院 薬学研究科 生物有機化学分野
〒565‐0871 大阪府吹田市山田丘1-6
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obika@phs.osaka-u.ac.jp