Cystein-Protease-Inhibitoren mit Aziridinstruktur

Fighting Parasites with Aziridines

Christoph Grathwol, Philipp Fey, Caroline Schad, Katharina Hilger, Stavroula Chartomatsidou

Mammalian and parasitic cysteine protease have been discovered as potential drug targets within the last two decades. The aziridine ring represents and electrophilic building block which is attacked by the cysteine residue of the protease’s active site. As a consequence, the nucleophilic ring opening reaction can lead to irreversible enzyme alkylation. The aim of our work is the increasing of water solubility of former promising compounds and the clarification of the binding mode. The expression of Rhodesain as target enzyme and the development of novel synthethic strategies to obtain covalent-reversible inhibitors is part of the thesis of Christoph Grathwol.