24th EUFEPS Talks

We want to invite you to the 24th EUFEPS Talks on September 15, 2025 at 4 pm CEST.

Stefan Knapp will give a talk with the title: "Targeting new E3 Ligases and validating them for PROTAC development".

Abstract:

The human E3 ligase family is a large and diverse family of proteins that has not been widely explored for the development of ligands and PROTACs (PROtein Targeting Chimeras). In this talk I will discuss strategies for the identification of new ligands using E-ASMS (enantiomer-selective affinity screening by MS), DEL-ML (DNA-encoded library screening coupled to machine learning) as well as strategies for the validation of E3 ligands for the development of the next generation of degraders.

References:

 Crystallographic fragment screening reveals ligand hotspots in TRIM21 PRY-SPRY domain.

Kim Y, Lučić A, Lenz C, Farges F, Schwalm MP, Saxena K, Hanke T, Marples PG, Aschenbrenner JC, Fearon D, von Delft F, Krämer A, Knapp S. Commun Chem. 2025 Jun 13;8(1):185. doi: 10.1038/s42004-025-01574-3.

Workflow for E3 Ligase Ligand Validation for PROTAC Development.

Miletić N, Weckesser J, Mosler T, Rathore R, Hoffmann ME, Gehrtz P, Schlesiger S, Hartung IV, Berner N, Wilhelm S, Müller J, Adhikari B, Němec V, Sivashanmugam SA, Elson L, Holzmann H, Schwalm MP, Hoffmann L, Abdul Azeez KR, Müller S, Kuster B, Wolf E, Đikić I, Knapp S. ACS Chem Biol. 2025 Feb 21;20(2):507-521. doi: 10.1021/acschembio.4c00812. Epub 2025 Feb 11.

Enantioselective Protein Affinity Selection Mass Spectrometry (EAS-MS).

Wang X, Sun J, Ahmad S, Yang D, Li F, Chan UH, Zeng H, Simoben CV, Houliston S, Dong A, Bolotokova A, Gibson E, Kutera M, Ghiabi P, Kondratov I, Matviyuk T, Chuprina A, Mavridi D, Lenz C, Joerger AC, Brown BD, Heath RB, Yue WW, Robbie LK, Beyett TS, Müller S, Knapp S, Harding R, Schapira M, Brown PJ, Santhakumar V, Ackloo S, Arrowsmith CH, Edwards AM, Peng H, Halabelian L. bioRxiv [Preprint]. 2025 Jan 22:2025.01.17.633682. doi: 10.1101/2025.01.17.633682.

Functional Characterization of Pathway Inhibitors for the Ubiquitin-Proteasome System (UPS) as Tool Compounds for CRBN and VHL-Mediated Targeted Protein Degradation.

Schwalm MP, Menge A, Elson L, Greco FA, Robers MB, Müller S, Knapp S. ACS Chem Biol. 2025 Jan 17;20(1):94-104. doi: 10.1021/acschembio.4c00450. Epub 2025 Jan 3.

PROTAC-mediated degradation reveals a non-catalytic function of AURORA-A kinase.

Adhikari B, Bozilovic J, Diebold M, Schwarz JD, Hofstetter J, Schröder M, Wanior M, Narain A, Vogt M, Dudvarski Stankovic N, Baluapuri A, Schönemann L, Eing L, Bhandare P, Kuster B, Schlosser A, Heinzlmeir S, Sotriffer C, Knapp S, Wolf E. Nat Chem Biol. 2020 Nov;16(11):1179-1188. doi: 10.1038/s41589-020-00652-y.

CV of Stefan Knapp:

Stefan Knapp studied chemistry at the University of Marburg (Germany) and the University of Illinois (USA). He received his Ph.D. in protein crystallography from the Karolinska Institute in Stockholm. He joined Pharmacia (Nerviano, Italy) in 1999 and left the company in 2004 to establish a research group at the Structural Genomics Consortium at the University of Oxford. From 2008 to 2015 he was Professor of Structural Biology at Oxford University (UK) and from 2012 to 2015 Director of Chemical Biology at the Target Discovery Institute at Oxford University. In 2015, he joined the University of Frankfurt as Professor of Pharmaceutical Chemistry. Since 2017, he is also the CSO of the SGC (Structure Genomics Consortium) node at Goethe University Frankfurt. His research interests are the elucidation of molecular/structural mechanisms of kinase regulation using high resolution structures, the design of selective kinase inhibitors, and the inhibition of protein interaction domains including bromodomains, which are the main readers of the epigenetic acetylation code, and E3 ligases.

Registration:

A registration is needed for this event. Please use the following link: https://us06web.zoom.us/meeting/register/UcIZO9LASCWDO7T2XcKByg. After the registration you will receive an E-Mail with the log-in details.