title: An organometallic inhibitor for the human repair enzyme 7,8-dihydro-8-oxoguanosine triphosphatase.
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.
authors.affiliation: Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Strasse, 35043 Marburg (Germany).
authors.forename: Manuel
authors.initials: M
authors.lastname: Streib
authors.forename: Katja
authors.initials: K
authors.lastname: Kräling
authors.forename: Kristin
authors.initials: K
authors.lastname: Richter
authors.forename: Xiulan
authors.initials: X
authors.lastname: Xie
authors.forename: Holger
authors.initials: H
authors.lastname: Steuber
authors.forename: Eric
authors.initials: E
authors.lastname: Meggers
mesh_terms: D045643:DNA Repair Enzymes / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry* / Q000494:pharmacology; D012428:Ruthenium / Q000737:chemistry*
chemical_list: D009942:Organometallic Compounds; D012428:Ruthenium; D010744:Phosphoric Monoester Hydrolases; C078207:8-oxodGTPase; D045643:DNA Repair Enzymes
keywords: 7,8-dihydro-8-oxoguanosine triphosphatase; enzyme inhibitors; organometallic compounds; protein crystal structures; ruthenium