Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Strasse, 35043 Marburg (Germany).
Angew Chem Int Ed Engl. 2014 Jan 3;53(1):305-9. doi: 10.1002/anie.201307849. Epub 2013 Nov 20.
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.
本文介绍了首例修复酶 8-氧鸟苷三磷酸酶（MTH1）小分子抑制剂的基于探针的发现，这是一种非传统的环金属化钌半夹心配合物。该金属有机抑制剂具有低纳摩尔的活性，表现出惊人的特异性，在对广泛的蛋白激酶和其他 ATP 结合蛋白的测试中得到了验证。通过蛋白质晶体学研究了金属有机抑制剂与 MTH1 的结合。
