Tom Brown Group

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

W. Doherty, E. Dürr, H. T. Baddock, S. Y. L, P. J. McHugh, T. Brown, M. O. Senge, E. M. Scanlana and J. F. McGouran. Org. Biomol. Chem. 2019.

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.