Protein-protein interactions (PPIs) play key role in many cellular processes including pathological conditions such as cancer progression. Selective control over therapeutically relevant PPIs would lead to better understanding of their function and could serve as starting points for drug discovery. PPIs in which the binding energy is distributed across a large interaction interface are especially challenging to target using small molecules. Protein surface mimetics, such as peptidomimetics are attractive alternative scaffolds but their development is a challenging task. One of our approaches is to rationally design inhibitors based on prior structural information and chemically modify a known binder with the goal of improve its properties. We also follow a bottom-up strategy where we use short folded sequences constructed from beta amino acids (beta peptide foldamers) as local protein surface mimetics, which can be considered as fragments of a large protein surface. Using these approaches we develop screening methods, ligand optimization strategies and compounds targeting different PPIs relevant in disease.
Selected publications
Promiscuity Mapping of the S100 Protein Family Using a High-Throughput Holdup Assay. Simon, M. A.; Bartus, É.; Mag, B.; Boros, E.; Roszjár, L.; Gógl, G.; Travé, G.; Martinek, T. A.; Nyitray, L. Sci. Rep. 2022, 12 (1), 5904.
Proteomimetic Surface Fragments Distinguish Targets by Function. Tököli, A.; Mag, B.; Bartus, É.; Wéber, E.; Szakonyi, G.; Simon, M. A.; Czibula, Á.; Monostori, É.; Nyitray, L.; Martinek, T. A. Chem. Sci. 2020, 11 (38), 10390–10398.
Structural Optimization of Foldamer-Dendrimer Conjugates as Multivalent Agents against the Toxic Effects of Amyloid Beta Oligomers. Bartus, É.; Olajos, G.; Schuster, I.; Bozsó, Z.; Deli, M. A.; Veszelka, S.; Walter, F. R.; Datki, Z.; Szakonyi, Z.; Martinek, T. A.; Fülöp, L. Molecules 2018, 23 (10)
De Novo Modular Development of a Foldameric Protein–Protein Interaction Inhibitor for Separate Hot Spots: A Dynamic Covalent Assembly Approach. Bartus, É.; Hegedüs, Z.; Wéber, E.; Csipak, B.; Szakonyi, G.; Martinek, T. A. ChemistryOpen 2017, 6 (2), 236–241.
