X-ray structural analysis

The elucidation and characterization of the structure and interaction relationships of proteins (targets) with drug molecules and, based on this, the further development of drugs is an important component in the establishment of new molecular strategies for the treatment of diseases, but also in the further development of other protein-based approaches.

Within the framework of the project, four subprojects are being worked on. In order to be able to answer the specific questions in each case, the protein structure of one or more targets will be solved experimentally by X-ray structure analysis. These findings will then serve as the basis for further research approaches and developments.

Specifically, the project is investigating, among other things, the binding modes of novel, proprietary active drugs by solving the complex structures of human glutaminyl cyclase and Meprin beta each with corresponding drug molecules. This is a prerequisite for developing patentable prototypes  which could be used for early therapy of Alzheimer's disease.

Furthermore, the focus is on the shape of the binding pocket of a monoclonal antibody, which is also of interest for the treatment of Alzheimer's disease. The specific binding properties are to be derived from the data obtained here as a basis for further biochemical evaluation and subsequently humanization.

In a third part of the project, the project team is conducting research on the proteinogenic sweeteners thaumatin II and brazzein. Obtained from novel production sources, they are intended to serve as dietary supplements. The structure and important post-translational modifications are being verified in the project.

Another object of investigation is lectins. Currently, several lectin-based product candidates for nasal application are undergoing clinical trials to protect against infection with corona and influenza viruses. In order to be able to make statements about the shape and details at the molecular level, a structure elucidation and binding characterization will be carried out for the first time within the scope of the project.

The project "Establishment and testing of effective methods for the investigation of structure-activity relationships using protein crystallography (EtaPPro)" is supported by the state of Saxony-Anhalt with funding from the European Regional Development Fund (ERDF).

Cancer is characterised by the migration of cells and the invasion of healthy tissues. This metastasis significantly impacts mortality. Remodelling of the extracellular matrix forms the key to the release of cells from the primary tumour and the migration to the sites at which metastases form. Meprin α is a metalloproteinase involved in these processes. The impact of Meprin activity on the migration and invasiveness of tumour cells has already been demonstrated.

As part of the “MeGrate – Validation of the proteinase Meprin α as antimigratory target in cancer” project, a research team from Fraunhofer IZI and headed by Dr Daniel Ramsbeck (head of the astacin proteases working group), is studying Meprin α as a drug target for various types of cancer together with researchers from the Institute for Molecular Medicine and Cell Research at the University of Freiburg. Their work focuses on breast, colon and liver cell cancer. Moreover, the researchers want to analyse the molecular structure of Meprin α in the complex with potent inhibitors. After successful target validation, this is intended to facilitate the optimisation of Meprin inhibitors in subsequent drug development projects.

This project was sponsored by the German Federal Ministry of Education and Research from 1 May 2020 to 30 April 2022.