Synthesis of Therapeutic Oligonucleotides

Description

This book presents the latest knowledge on a broad range of topics relating to the synthesis of natural and artificial oligonucleotides with therapeutic potential. Nucleic acid-based therapeutics are attracting much attention, and numerous therapeutic oligonucleotides, such as antisense oligonucleotides, siRNAs, splice-switching oligonucleotides, and nucleic acid aptamers, are being evaluated in clinical trials for the treatment of a variety of diseases. Synthesis of Therapeutic Oligonucleotides covers a broad range of topics in the field that are of high relevance to researchers, including the synthesis of natural and chemically modified oligonucleotides, the development of novel nucleic acid analogs, industrial scale synthesis and purification of oligonucleotides, and important aspects of chemistry, manufacturing, and controls (CMC). The aim is to provide new insights and inspire fresh ideas in nucleic acid chemistry that may ultimately lead to novel concepts and techniques and the discovery of more effective nucleic acid drugs. The book will be of high value for both established researchers in the field and students intending to specialize in nucleic acid chemistry research. Front Matter ....Pages i-viii Front Matter ....Pages 1-1 Non-protected Synthesis of Oligonucleotides (Akihiro Ohkubo, Kohji Seio, Mitsuo Sekine)....Pages 3-16 Various Coupling Agents in the Phosphoramidite Method for Oligonucleotide Synthesis (Masaki Tsukamoto, Yoshihiro Hayakawa)....Pages 17-39 Recent Development of Chemical Synthesis of RNA (Mitsuo Sekine)....Pages 41-65 RNA Synthesis Using the CEM Group (Hidetoshi Kitagawa)....Pages 67-81 Liquid-Phase Synthesis of Oligonucleotides (Satoshi Katayama, Kunihiro Hirai)....Pages 83-95 Large-Scale Oligonucleotide Manufacturing (Eduardo Paredes, Tatsuya Konishi)....Pages 97-112 Front Matter ....Pages 113-113 Nucleosides and Oligonucleotides Incorporating 2-Thiothymine or 2-Thiouracil Derivatives as Modified Nucleobases (Kohji Seio, Mitsuo Sekine)....Pages 115-130 Site-Specific Modification of Nucleobases in Oligonucleotides (Yoshiyuki Hari)....Pages 131-145 Four-Hydrogen-Bonding Base Pairs in Oligonucleotides: Design, Synthesis, and Properties (Noriko Saito-Tarashima, Akira Matsuda, Noriaki Minakawa)....Pages 147-169 Photo-Cross-Linkable Artificial Nucleic Acid: Synthesis and Properties of 3-Cyanovinylcarbazole-Modified Nucleic Acids and Its Photo-Induced Gene-Silencing Activity in Cells (Takashi Sakamoto, Kenzo Fujimoto)....Pages 171-186 Effects of 2′-O-Modifications on RNA Duplex Stability (Yoshiaki Masaki, Akihiro Ohkubo, Kohji Seio, Mitsuo Sekine)....Pages 187-199 2′,4′-Bridged Nucleic Acids Containing Plural Heteroatoms in the Bridge Moiety (Yoshiyuki Hari, Satoshi Obika)....Pages 201-221 Synthesis and Therapeutic Applications of Oligonucleotides Containing 2′-O,4′-C-Ethylene- and 3′-O,4′-C-Propylene-Bridged Nucleotides (Koji Morita, Makoto Koizumi)....Pages 223-232 RNA Bioisosteres: Chemistry and Properties of 4′-thioRNA and 4′-selenoRNA (Noriaki Minakawa, Noriko Saito-Tarashima, Akira Matsuda)....Pages 233-252 Development of Triplex Forming Oligonucleotide Including Artificial Nucleoside Analogues for the Antigene Strategy (Yosuke Taniguchi, Shigeki Sasaki)....Pages 253-269 Chemical Synthesis of Boranophosphate Deoxy-ribonucleotides (Yohei Nukaga, Takeshi Wada)....Pages 271-284