Scorpionate Complexes Suitable for Enzyme Inhibitor Studies

Nina   Victoria   Fischer; Gazi      Turkoglu; Nicolai      Burzlaff

Abstract

The review starts with a brief summary on pharmaceutical relevant mononuclear zinc and non heme iron enzymes, with a main focus on zincins such as the angiotensin converting enzyme (ACE). Different approaches to classify such enzymes will be discussed. Especially, the main features of the metal binding motifs are highlighted. Recent advances in coordination chemistry with the purpose to mimic these features by small molecule ligands and metal complexes thereof are referred. The review then focuses on current developments in inhibitor studies based on such structural models. Exemplary, tripodal model complexes for matrix metalloproteinases (MMPs) are summarised, which have been successfully applied in identifying new inhibitors e.g. for zincins. Several recently developed inhibitors as well as their coordination modes towards zinc will be reflected. The report will further focus on the quest for new zinc binding groups (ZBGs) in respect of zincin inhibitors. Such novel and up to now rather uncommon ZBGs might have a huge impact on new lead structures in pharmaceutical research. It will be discussed how the model complexes are currently improved by mimicking also the hydrogen bridges in the enzymes active site. Finally, in some sort of perspective, a similar approach for mononuclear non heme iron oxygenases will be discussed.