Doxifluridine-conjugated 2-5A analog shows strong RNase L activation ability and tumor suppressive effect

作者：Kitamura Yoshiaki; Kito Seiya; Nakashima Remi; Tanaka Katsuki; Nagaoka Kumi; Kitade Yukio^*

来源：Bioorganic & Medicinal Chemistry, 2016, 24(16): 3870-3874.

DOI：10.1016/j.bmc.2016.06.033

• 2-5A
• RNase L
• 8-Methyladenosine
• Binding site
• Doxifluridine

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.

• 出版日期2016-8-15