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A hydroxamic-acid-containing nucleoside inhibits DNA repair nuclease SNM1A.

ABSTRACT: 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.

SUBMITTER: Doherty W

PROVIDER: S-EPMC6984127 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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A hydroxamic-acid-containing nucleoside inhibits DNA repair nuclease SNM1A.

Doherty William W Dürr Eva-Maria EM Baddock Hannah T HT Lee Sook Y SY McHugh Peter J PJ Brown Tom T Senge Mathias O MO Scanlan Eoin M EM McGouran Joanna F JF

Organic & biomolecular chemistry 20190805 35

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. ...[more]

PMID: 31380542

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