Labelling and Manipulating Biomolecules with Light

Nadja A. Simeth / University of Göttingen, Germany

March 13, 2025, 3:00–4:00 pm CET

Online live talk

Introduction

In recent years, light has been employed as an external stimulus to photocontrol diverse processes in various fields ranging from material science to biology. This approach relies on the use of small, light-responsive molecules that undergo a structural change upon irradiation, generating different functional states from a single molecule. By attaching suitable substituents to such photoactuators, these molecules can be embedded into biomacromolecules to link their structural change to a change in the biomolecule’s properties.
For instance, the secondary structure motifs present in peptides dictate their properties and supramolecular interactions. As they are highly sensitive to mini-mal structural changes, it is possible to affect their folding and thus their charac-teristics by small, stimuli-responsive alterations. This would allow for new synthetic model peptides to be generated, in which, for instance, peptide-protein interactions or peptide self-assembly processes could be spatio-temporally controlled, addressing the issue of lacking temporal resolution in classical models.
In this work, we incorporate photoswitches, i.e. molecules that isomerize back and forth between two forms changing their characteristics, as unnatural amino acids (UAAs) into peptide helices and hairpin structures to reversibly (un)fold them by light. We will show how we can use these molecules to control supramolecular interactions, including disease-correlated peptide aggregation with unprecedented spatiotemporal resolution using a combination of spectroscopy and microscopy techniques.

Nadja A. Simeth

was born in Cham, Bavaria, Germany. She started in 2009 with her studies in chemistry at the University of Regensburg, Germany, and graduated in 2014 after working with Morten Grotli at the University of Gothenburg, Sweden, for her Master's project. Then, she pursued her doctorate studies with Burkhard König at the University of Regensburg, Germany, as a fellow of the Studienstiftung des Deutschen Volkes. In 2017, she was a visiting researcher with Maurizio Fagnoni at the PhotoGreenLab at the University of Pavia, Italy. She returned to Regensburg and defended her thesis in summer 2018 with summa cum laude. She afterwards joined the group of Ben L. Feringa at the University of Groningen as a postdoc supported by a Feodor-Lynen Fellowship of the Humboldt Foundation. In autumn 2021, she was appointed as assistant professor at the University of Göttingen. She is interested in the design of smart drugs, biochemical probes and labels, as well as photoresponsive supramolecular architectures and biohybrid systems. The current research of the lab spans all thy way from developing small, organic photoactuators to the design and synthesis of stimuli-responsive peptides under the umbrella "PhotoBioOrgChem".