Device for the Mesurement of Biomolecular-Interactions

• Subject Area: Biological Chemistry and Food Chemistry
• Term: Funded in 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 560003967

Optical biosensors are a standard tool for analyzing the interaction between two binding partners, for example in medicinal chemistry. They are based on the immobilization of an interaction partner on a sensor against which an analyte is titrated. When the analyte binds to its binding partner, there is a change in the refractive index of the sensor. This makes the kinetic parameters of a binding experimentally accessible in addition to the affinity. Grating-coupled interferometry (GCI) is a more recent development in this field. It is based on refractive index changes within an evanescent field at the sensor surface caused by the binding of an analyte. In contrast to SPR, GCI generates such a field along the entire length of the sensor. This leads to more available binding events contributing to the signal and thus to a higher sensitivity compared to SPR. GCI allows the analysis of molecular interactions in a wide size range of interacting molecules. This includes macromolecules such as proteins and nucleic acids, as well as their complexes; peptides and oligonucleotides; drug-like molecules (molecular weight approx. 500 Da) down to small organic compounds (so-called fragments, MW < 300 Da). Due to the increased sensitivity of GCI, it offers the possibility of detecting small, mostly low-affinity molecules, such as those used in fragment-based drug discovery. The establishment of such a device, which was previously lacking at the University of Würzburg, as part of the newly appointed W3 professorship at the Chair of Pharmaceutical and Medicinal Chemistry at the Institute of Pharmacy and Food Chemistry at the University of Würzburg (Brunschweiger working group) will support or enable numerous projects in the search for new bioactive compounds. The device will be used for the validation of drug candidates from the screens of DNA-encoded molecule libraries. Above all, it will be used in collaborative projects in the context of fragment-based drug discovery, which has become a focus at JMU in recent years. In the field of macromolecular interactions, the device will enable the characterization of RNA-protein interactions, for example in the development of new PROTAC modalities. Furthermore, the interaction of peptides and therapeutic proteins such as cytokines and growth factors as well as their polymer conjugates with receptors will be investigated. The characterization of larger particle structures, such as those used as vehicles for mRNA vaccines and active substances, includes the investigation of the accessibility of ligands that are attached to the surface of polymers.

• DFG Programme: Major Research Instrumentation
• Major Instrumentation: Gerät zur Messung Biomolekularer-Interaktionen
• Instrumentation Group: 3160 Biomolekular-Interaktionssysteme
• Applicant Institution: Julius-Maximilians-Universität Würzburg
• Leader: Professor Dr. Andreas Brunschweiger