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oai:figshare.com:article/34039039 2026-10-01T05:11:37Z category_4 category_14 category_19 category_21 category_873 category_39 category_64 category_122 category_132 category_134 category_135 portal_63 item_type_6 month_year_10_2026

Substrate Selectivity of Viperin Probed Using Anticancer-Related Pyrimidine Nucleotide Analogs Minshik Jo (13163182) Victor Rivera-Santana (25152361) Hanyu Su (18202420) Dillon P. Langford (18266687) E. Neil G. Marsh (8378205) Biochemistry Molecular Biology Pharmacology Biotechnology Chemical Sciences not elsewhere classified Ecology Cancer Mental Health Infectious Diseases Virology Computational Biology generally high specificity elicited reductive cleavage 3 ′- fluoroctp 3 ′- deoxy natural antiviral nucleotide various drugs mimic antiviral enzyme drugs may anticancer drugs triphosphate forms substrate selectivity rna replication pyrimidine nucleosides last compound gemcitabine triphosphate examined whether either dna dehydrated products dehydrated product ddhctp ), autoimmune diseases Many antiviral and anticancer drugs are based on the structure of pyrimidine nucleosides. Once phosphorylated, they function by interfering with either DNA or RNA replication or transcription. The antiviral enzyme, viperin, catalyzes the dehydration of CTP to produce 3′-deoxy-3′,4′-didehydroCTP (ddhCTP), which functions as a natural antiviral nucleotide. Various drugs mimic the structure of CTP, and furthermore, viperin is upregulated in some cancers and autoimmune diseases. Therefore, we examined whether such drugs may be substrates for viperin. A panel of eight commercially available nucleosides, including several clinically used drugs, were enzymatically converted to their triphosphate forms and investigated as substrates for viperin. Five of the nucleotides were not substrates, indicating that viperin has generally high specificity for CTP. Two nucleotides, 3′-deoxy-3′-fluoroCTP and cytarabine triphosphate elicited reductive cleavage of SAM and were converted to their dehydrated products by viperin. The last compound, gemcitabine triphosphate, elicited reductive cleavage of SAM, but no dehydrated product was observed, implying that it activates SAM cleavage without undergoing hydrogen atom abstraction. The implications of these results are discussed. 2026-10-01T00:00:00Z Text Journal contribution 10.1021/acs.biochem.6c00226.s001 https://figshare.com/articles/journal_contribution/Substrate_Selectivity_of_Viperin_Probed_Using_Anticancer-Related_Pyrimidine_Nucleotide_Analogs/34039039 CC BY-NC 4.0