title: Synthesis of scpBNA-mC, -A, and -G Monomers and Evaluation of the Binding Affinities of scpBNA-Modified Oligonucleotides toward Complementary ssRNA and ssDNA.
abstract: We previously reported the synthesis and evaluation of 2'-O,4'-C-spirocyclopropylene-bridged nucleic acid (scpBNA) bearing a thymine (T) nucleobase. Oligonucleotides (ONs) modified with scpBNA-T exhibited strong binding affinity to complementary single-stranded RNA (ssRNA) and high enzymatic stability. These biophysical properties suggest that scpBNAs are well suited for use in antisense strategies. Herein, we describe the synthesis of scpBNA monomers bearing 5-methylcytosine (mC), adenine (A), and guanine (G) nucleobases for use in a variety of sequences. The prepared scpBNA monomers were incorporated into ONs at various positions. The scpBNA-modified ONs exhibited excellent duplex-forming ability with the complementary ssRNA comparable to ONs modified with 2'-O,4'-C-methylene-bridged nucleic acid (2',4'-BNA/LNA). Moreover, ON modified with scpBNA-mC, -A, and -G showed higher enzymatic stability than the corresponding 2',4'-BNA/LNA-modified ON. These results demonstrated a promising role for the incorporation of scpBNA monomers into therapeutic antisense ONs.
authors: Graduate School of Pharmaceutical Sciences, Osaka University , 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.|Core Research for Evolutional Science and Technology (CREST), Japan Sciences and Technology Agency (JST) , 7 Gobancho, Chiyoda-ku, Tokyo 102-0076, Japan.
authors: Masahiko
authors: M
authors: Horiba
authors: Graduate School of Pharmaceutical Sciences, Osaka University , 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.|Core Research for Evolutional Science and Technology (CREST), Japan Sciences and Technology Agency (JST) , 7 Gobancho, Chiyoda-ku, Tokyo 102-0076, Japan.
authors: Takao
authors: T
authors: Yamaguchi
authors: Graduate School of Pharmaceutical Sciences, Osaka University , 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.|Core Research for Evolutional Science and Technology (CREST), Japan Sciences and Technology Agency (JST) , 7 Gobancho, Chiyoda-ku, Tokyo 102-0076, Japan.
authors: Satoshi
authors: S
authors: Obika
mesh_terms: D001665:Binding Sites; D004277:DNA, Single-Stranded / Q000737:chemistry*; D009696:Nucleic Acids / Q000737:chemistry*; D009841:Oligonucleotides / Q000737:chemistry*; D012313:RNA / Q000737:chemistry*; D013057:Spectrum Analysis / Q000379:methods
chemical_list: D004277:DNA, Single-Stranded; D009696:Nucleic Acids; D009841:Oligonucleotides; D012313:RNA