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Keywords:

  • 7,8-dihydro-8-oxoguanosine triphosphatase;
  • enzyme inhibitors;
  • organometallic compounds;
  • protein crystal structures;
  • ruthenium

Abstract

The probe-based discovery of the first small-molecule inhibitor of the repair enzyme 8-oxo-dGTPase (MTH1) is presented, which is an unconventional cyclometalated ruthenium half-sandwich complex. The organometallic inhibitor with low-nanomolar activity displays astonishing specificity, as verified in tests with an extended panel of protein kinases and other ATP binding proteins. The binding of the organometallic inhibitor to MTH1 is investigated by protein crystallography.