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Mechanism of the extremely high duplex-forming ability of oligonucleotides modified with N-tert-butylguanidine- or N-tert-butyl-N'- methylguanidine-bridged nucleic acids.
Yamaguchi, Takao; Horie, Naohiro; Aoyama, Hiroshi; Kumagai, Shinji; Obika, Satoshi.
Afiliación
  • Yamaguchi T; Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
  • Horie N; Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
  • Aoyama H; Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
  • Kumagai S; Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Shonan Health Innovation Park, 2-26-1 Muraoka-Higashi, Fujisawa, Kanagawa 251-8555, Japan.
  • Obika S; Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Nucleic Acids Res ; 51(15): 7749-7761, 2023 08 25.
Article en En | MEDLINE | ID: mdl-37462081
Antisense oligonucleotides (ASOs) are becoming a promising class of drugs for treating various diseases. Over the past few decades, many modified nucleic acids have been developed for application to ASOs, aiming to enhance their duplex-forming ability toward cognate mRNA and improve their stability against enzymatic degradations. Modulating the sugar conformation of nucleic acids by substituting an electron-withdrawing group at the 2'-position or incorporating a 2',4'-bridging structure is a common approach for enhancing duplex-forming ability. Here, we report on incorporating an N-tert-butylguanidinium group at the 2',4'-bridging structure, which greatly enhances duplex-forming ability because of its interactions with the minor groove. Our results indicated that hydrophobic substituents fitting the grooves of duplexes also have great potential to increase duplex-forming ability.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Oligonucleótidos / Guanidinas / Metilguanidina Idioma: En Revista: Nucleic Acids Res Año: 2023 Tipo del documento: Article País de afiliación: Japón

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Oligonucleótidos / Guanidinas / Metilguanidina Idioma: En Revista: Nucleic Acids Res Año: 2023 Tipo del documento: Article País de afiliación: Japón