Alternative metal binding groups in drugs for the treatment of periodontitis – AMePA

Many pharmaceutically interesting proteins bear metal ions that are either necessary for accurate protein folding or essential for enzyme functionality in the first place. Targeting such metal–dependent enzymes include e.g. the binding of the potential drug molecule to the corresponding metal, whereas Zink is one of the most prominent ions. This is also the case for bacterial Glutaminyl Cyclase of Type II from P. gingivalis, one of the most abundant periodontal pathogens causing periodontitis. For the development of new therapeutic approaches, the generation of patentable new compounds is of high interest, whereas the most critical point is the generation of new metal binding groups (MBGs) for the binding to the enzyme’s Zink-ion. There are only a few MBGs known. To broaden the available chemical space synthesis and testing of new potential MBGs is therefore essential. In AMePA, new chemical entities are developed and tested in biochemical assays. Those prototypes will be expanded with more examples using in-house established chemistry in a joint project with Fraunhofer IZI-MWT. 

The project, which started on December 7th, 2020, will run until July 31st, 2022, and is funded by the German Federal State of Saxony-Anhalt with funds from the European Regional Development Fund (ERDF).