Deploying solid-phase synthesis to access thymine-containing nucleoside analogs that inhibit DNA repair nuclease SNM1A†,10.1039/D3OB00836C

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Deploying solid-phase synthesis to access thymine-containing nucleoside analogs that inhibit DNA repair nuclease SNM1A†

Christine A. Arbour,Ellen M. Fay,Joanna F. McGouran,Barbara Imperiali

Organic & Biomolecular Chemistry Pub Date : 06/26/2023 00:00:00 , DOI:10.1039/D3OB00836C

Abstract

Nucleoside analogs show useful bioactive properties. A versatile solid-phase synthesis that readily enables the diversification of thymine-containing nucleoside analogs is presented. The utility of the approach is demonstrated with the preparation of a library of compounds for analysis with SNM1A, a DNA damage repair enzyme that contributes to cytotoxicity. This exploration provided the most promising nucleoside-derived inhibitor of SNM1A to date with an IC₅₀ of 12.3 μM.