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

  • Org Biomol Chem. 2023 Jul 19;21(28):5873-5879. doi: 10.1039/d3ob00836c.
Christine A Arbour  1 ,  Ellen M Fay  2 ,  Joanna F McGouran  2 ,  Barbara Imperiali  1
Affiliations
  • 1. Department of Biology and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. [email protected].
  • 2. School of Chemistry and Trinity Biomedical Sciences Institute, Trinity College Dublin, 152-160 Pearse St., Dublin 2, Ireland.
PMID: 37417819 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.

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