If protein kinases get in touch with tumor promotors, they accelerate the growth of tumor cells. This influence of deregulation of kinases can be blocked by inhibitors. Currently, the most effective kinase inhibitor is staurosporine. As it is toxic, it cannot be used as a drug itself. But staurosporine is used as a precursor to find kinase inhibitors with chemically similar structure and good inhibitor efficacy. Searching for physiologically compatible and specific inhibitors is important in drug design to develop novel anti-cancer drugs. In my doctoral thesis, I develop screening methods to promote the fundamental research of drug design in this field of science.
I develop an optical sensor to compare inhibitor constants between various inhibitors (partly already in clinical use) and different protein kinases: reflectometric interference spectroscopy and 1-lamda spectroscopy can determine intermolecular interactions between kinases and inhibitors in a time-resolved and label-free manner.
By developing the sensor, diverse iterations of the modification of the sensor surface are necessary to receive a high specificity. For different inhibitors, different methods have to be developed to covalently link them to the sensor surface. Afterwards, kinase- and inhibitorscreenings can be conducted by a binding inhibition test.
For kinse identification as well as the determination of the interaction sites between kinases and inhibitor, mass spectrometric analysis is conducted.
The combination of the optical sensor with a protein analysis via MS leads to a qualitative and quantitative screening method for protein kinases and inhibitors.

Co-operation partner:
Company Merck in Darmstadt, analytical department
Working group Prof. Gauglitz

Teaching:
Practical training: physical chemistry für bioinformatics
Tutorial: physical chemistry for bioinformatics
Tutorial: physical chemistry for biochemistry
Practical training module: analytical chemistry