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A hydroxamic-acid-containing nucleoside inhibits DNA repair nuclease SNM1A. 2019
William Doherty, and
Eva-Maria Dürr, and
Hannah T Baddock, and
Sook Y Lee, and
Peter J McHugh, and
Tom Brown, and
Mathias O Senge, and
Eoin M Scanlan, and
Joanna F McGouran
School of Chemistry and Trinity Biomedical Sciences Institute, Trinity College Dublin, 152-160 Pearse St, Dublin 2, Ireland. jmcgoura@tcd.ie.
Nine modified nucleosides, incorporating zinc-binding pharmacophores, have been synthesised and evaluated as inhibitors of the DNA repair nuclease SNM1A. The series included oxyamides, hydroxamic acids, hydroxamates, a hydrazide, a squarate ester and a squaramide. A hydroxamic acid-derived nucleoside inhibited the enzyme, offering a novel approach for potential therapeutic development through the use of rationally designed nucleoside derived inhibitors.
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