Aarhus University Seal

Department of Chemistry Seminar Series: Prof. Tom Grossmann, VU Amsterdam (Host: Thomas B. Poulsen)

Passing cellular membranes with biomimetics – another holy grail or just the final frontier?

Info about event


Thursday 22 February 2024,  at 15:00 - 16:00


1514-213, Aud I, Department of Chemistry, Langelandsgade 140

15:00-15:15       Coffee & cake in the foyer
15:15-16:00       Scientific talk in Auditorium I

Speaker: Prof. Tom Grossmann, VU Amsterdam

A large number of therapeutically attractive target proteins is shielded by cellular membranes. Many of these targets turned out to be undruggable with small molecules and due to membrane shielding they are not accessible with large biologics. This triggered the search for molecules which combine the enhanced surface recognition capabilities of biologics with the ability to penetrate cellular membranes. A promising strategy towards this goal involves the use of protein-inspired scaffolds that recapitulate small tertiary structures and facilitate miniaturization to support cellular uptake. Proteins are natural scaffolds defined by a hierarchy of structural complexity and have evolved to manifest unique functional characteristics e.g., molecular recognition properties that enable high binding affinity and selectivity.[1,2] Utilizing these features, proteins have been used as a starting point for the design of bioactive reagents in drug discovery. The lecture will describe design approaches towards bioactive proteomimetics using a human oncogene[3] and a bacterial target protein[4] as example. In both cases, the installation of cell permeability was essential for achieving bioactivity.

1  M. Pelay-Gimeno, A. Glas, O. Koch, T. N. Grossmann,
   Angew. Chem. Int. Ed., 54, 8896 (2015).
2  W. S. Horne, T. N. Grossmann, Nature Chem., 12, 331 (2020).
3  M. Wendt et al., Angew. Chem. Int. Ed., 60, 13937 (2021)
4  F. M. Paulussen et al., J. Am. Chem. Soc., 144, 15303 (2022)