Bachem AtPS Award for Peptide Science for Peter ‘t Hart

Peter ‘t Hart, Group Leader at the Chemical Genomics Centre of the Max Planck Society in Dortmund received the Bachem AtPS Award for Peptide Science for his research on the Protein-RNA interactions, during the 12th Austrian Peptide Symposium on Dec. 5th, 2023, in Vienna, Austria. 

Research of the ’t Hart Group

Protein-RNA interactions are essential in the regulation and function of any given RNA. Aberrant formation of such interactions can therefore rapidly lead to disease making them attractive therapeutic targets. Targeting such interactions is challenging however since they involve large interfaces and typically lack well defined pockets.¹ To overcome this challenge, we take inspiration from strategies originally developed to identify protein-protein interaction inhibitors and adapt them for protein-RNA interaction inhibitors. The first strategy we used is structure-based design of stapled peptides as inhibitors of the splicing factor polypyrimidine-tract binding protein 1 (PTBP1).² These peptides were able to interfere with an intramolecular protein-protein interaction that allosterically regulates RNA-binding. By exploring various stapling strategies, an inhibitory peptide was identified that was stable against proteolysis as well as cell permeable and able to modulate splicing events regulated by PTBP1. When a given target lacks structural information a structure-based design approach can’t be used. To be able to identify inhibitors in this situation we use genetically encoded cyclic peptide libraries (i.e.: SICLOPPS) in combination with an in-house developed assay to screen for inhibitory peptides of the splicing factor hnRNP A2/B1.³ Preliminary data shows that hits can be found from a single screening round when combined with next generation sequencing and that structural optimization is feasible.

Peter ’t Hart

Peter ’t Hart studied drug innovation at the Utrecht Institute of Pharmaceutical Sciences where he also finished his doctoral studies. During his Postdoc in the Department of Prof. Herbert Waldmann at the Max Planck Institute of Molecular Physiology in Dortmund he developed cyclic peptide inhibitors of complexes involved in epigenetic regulation. Since 2018 he is group leader at the Chemical Genomics Centre of the Max Planck Society.

The Bachem AtPS Award is given to postdoctoral fellows and Junior Research Group Leaders who have made outstanding contributions to the chemistry or biology of peptides in the three years prior to nomination. The award is sponsored by Bachem AG.

The Bachem AtPS Award

1. D. M. Krüger, S. Neubacher and T. N. Grossmann, Protein–RNA interactions: structural characteristics and hotspot amino acids, RNA, 2018, 24, 1457–1465.
2. S. Schmeing, G. Amrahova, K. Bigler, J.-Y. Chang, J. Openy, S. Pal, L. Posada, R. Gasper and P. ’t Hart, Rationally designed stapled peptides allosterically inhibit PTBP1–RNA-binding, Chem. Sci., 2023, 14, 8269–8278.
3. A. Tavassoli, SICLOPPS cyclic peptide libraries in drug discovery, Curr. Opin. Chem. Biol., 2017, 38, 30–35.