Photo-dynamic ligands for oncology

Wilhelm Sander Foundation supports project by CENIDE members

The protein survivin helps tumor cells to survive conventional treatment methods. Molecular biologist Prof. Dr. Shirley Knauer and chemist Prof. Dr. Michael Giese from the University of Duisburg-Essen now want to develop dynamic, light-switchable ligand systems as novel survivin inhibitors. The Wilhelm Sander Foundation is funding the project with almost 190,000 euros for two years.

CENIDE members Prof. Shirley Knauer and Prof. Michael Giese are using their expertise in protein targeting using supramolecular guanidiniocarbonyl pyrrole (GCP) ligands for a new project. With their current project, they are specifically building on results from the Collaborative Research Center 1093 and are developing innovative strategies to inhibit survivin.

Survivin is a protein that helps tumor cells to escape programmed cell death and at the same time controls cell division in degenerated cells. Due to its lack of enzymatic activity and its role as an adapter for numerous interaction partners, survivin is considered particularly difficult to inhibit. Conventional small molecules, which are successfully used in cancer research, reach their limits here.

The protein is regulated by a complex and multifaceted interplay: "In particular, temporary changes in the protein structure and domain orientation influence the function of survivin in cell division. Survivin acts as part of the chromosomal passenger complex (CPC)," explains Prof. Knauer. "And this is where we now want to target it."

In previous projects, the researchers have already developed selective but static ligands for survivin. Now they are pursuing a dynamic approach: "In order to inhibit the dynamics of survivin even more efficiently, we want to create ligands that can be switched by light irradiation and that have several binding sites on the protein surface in the form of so-called multivalent GCP systems," says Prof. Giese.

The team plans to establish a modular system for the development of these novel ligand systems. The aim is to create a toolbox of building blocks that will make it possible to specifically influence the spatial orientation of biologically relevant protein domains. In the long term, this knowledge could not only advance basic research, but also serve as a basis for new therapeutic approaches for various types of tumors.

https://www.uni-due.de/cenide/en/news-detail.php?id=photo-dynamic-ligands-for-oncology