title: Doxifluridine-conjugated 2-5A analog shows strong RNase L activation ability and tumor suppressive effect.
abstract: RNase L is activated by 2',5'-oligoadenylates (2-5A) at subnanomolar levels to cleave single-stranded RNA. We previously reported the hypothesis that the introduction of an 8-methyladenosine residue at the 2'-terminus of the 2-5A tetramer shifts the 2-5A binding site of RNase L. In this study, we synthesized various 5'-modified 2-5A analogs with 8-methyladenosine at the 2'-terminus. The doxifluridine-conjugated 8-methyladenosine-substituted 2-5A analog was significantly more effective as an activator of RNase L than the parent 5'-monophophorylated 2-5A tetramer and showed a tumor suppressive effect against human cervical cancer cells.
authors.affiliation: Department of Biomolecular Science, Graduate School of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kitamura
authors.affiliation: Department of Biomolecular Science, Graduate School of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Seiya
authors.initials: S
authors.lastname: Kito
authors.affiliation: Department of Biomolecular Science, Graduate School of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Remi
authors.initials: R
authors.lastname: Nakashima
authors.affiliation: Department of Biomolecular Science, Graduate School of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Katsuki
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Kumi
authors.initials: K
authors.lastname: Nagaoka
authors.affiliation: Department of Biomolecular Science, Graduate School of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; Department of Applied Chemistry, Faculty of Engineering, Aichi Institute of Technology, 1247 Yachigusa, Yakusa-cho, Toyota, Aichi 470-0392, Japan. Electronic address: ykkitade@gifu-u.ac.jp.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kitade
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D004722:Endoribonucleases / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D005467:Floxuridine / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D013058:Mass Spectrometry; D066244:Proton Magnetic Resonance Spectroscopy
chemical_list: D000970:Antineoplastic Agents; D005467:Floxuridine; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease; C025034:doxifluridine
keywords: 2-5A; 8-Methyladenosine; Binding site; Doxifluridine; RNase L