Professor Matthias Gehringer
University of Tubingen
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Talk title: TBC
Biography: Matthias studied chemistry at the Karlsruhe Institute of Technology (KIT; Germany), the Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM; France), and the University of Heidelberg (Germany). He obtained his doctorate from the University of Tübingen (Germany) where he worked in the group of Prof. Stefan Laufer on reversible and irreversible inhibitors of the protein kinase JAK3. As a postdoc at the Swiss Federal Institute of Technology (ETH) Zürich (with Prof. Karl-Heinz Altmann), he focused on the total synthesis of complex natural products from the mycolactone family. In 2019, he was appointed as Assistant Professor for Medicinal Chemistry at the Institute of Pharmaceutical Sciences, University of Tübingen. In May 2024, he was appointed as Full Professor and head of the Division for Medicinal Chemistry at the Institute of Biomedical Engineering of the Faculty of Medicine, University of Tübingen. Matthias is a Principal Investigator (PI) in the Cluster of Excellence "Image Guided and Functionally Instructed Tumor Therapies (iFIT)".
His research focuses primarily on covalent protein kinase inhibitors and novel approaches for the covalent targeting of cysteine and other amino acids. He received a variety of awards including the Young Investigator Award of the German Pharmaceutical Society (DPhG) and the Phil Portoghese Lectureship Award of the American Chemical Society (ACS) MEDI division. Notably, Matthias is currently heading a European Federation for Medicinal Chemistry and Chemical Biology (EFMC) Best Practices initiative on covalent drug modalities.
Dr Stephan Hacker
University of Leiden
Tentative talk title: Profiling the proteome-wide selectivity of diverse electrophiles
Biography: Dr. Stephan Hacker performed his PhD studies with Prof. Andreas Marx at the University of Konstanz, Germany, and his postdoctoral research with Prof. Benjamin Cravatt at The Scripps Research Institute in La Jolla, USA. Afterwards, he moved to the Technical University of Munich, Germany, to work as an independent group leader. In 2021, he became an Assistant Professor at the Leiden Institute of Chemistry. Stephan Hacker’s group develops chemistries for novel covalent protein ligands targeting diverse amino acids as well as chemoproteomic technologies to study their target engagement with resolution of the modified amino acid residue in proteome-wide studies. His group focuses on the application of these compounds and technologies to identify new druggable target proteins in bacteria.
Abstract: Patrick R. A. Zanon, Fengchao Yu, Patricia Musacchio, Lisa Lewald, Michael Zollo, Kristina Krauskopf, Dario Mrdović, Patrick Raunft, Thomas E. Maher, Marko Cigler, Christopher Chang, Kathrin Lang, F. Dean Toste, Alexey I. Nesvizhskii, Stephan M. Hacker
Targeted covalent inhibitors are powerful entities in drug discovery to expand the druggable proteome. Nevertheless, their application has so far mainly been limited to addressing cysteine residues. The development of cysteine-directed covalent inhibitors has largely profited from determining their proteome-wide selectivity using competitive residue-specific proteomics. Several probes have recently been described to monitor other amino acids using this technology and many more electrophiles exist to modify proteins. Nevertheless, a direct, proteome-wide comparison of the selectivity of diverse probes is still entirely missing. Here, we developed a completely unbiased workflow to analyse electrophile selectivity proteome-wide and applied it to directly compare 54 alkyne probes containing diverse reactive groups. In this way, we verified and newly identified probes to monitor a total of nine different amino acids as well as the N terminus proteome-wide. This selection includes the first probes to globally monitor tryptophans, histidines and arginines as well as novel tailored probes for methionines, aspartates and glutamates.
More information about our speakers will be available soon.
