Doxifluridine-conjugated 2-5A analog shows strong RNase L activation ability and tumor suppressive effect
Yoshiaki Kitamura1, Seiya Kito2, Remi Nakashima2
1Department 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.
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.
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