Sebastian Pomplun Group

Drug discovery – Novel chemical modalities – Nucleic acid binding proteins

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Our Focus

The Pomplun Lab, led by Associate Professor Sebastian Pomplun, focuses on developing innovative chemical modalities to address challenging drug targets, with a particular emphasis on oncology. Key research directions include the creation of advanced technologies for high-throughput screening of synthetic libraries containing millions of drug-like compounds. This platform facilitates the identification of novel drug candidates by enabling the screening of not only classical small molecules but also peptidomimetics and macrocycles—an approach well-suited for targeting complex protein-protein and protein-nucleic acid interactions.  

In addition to high-throughput screening, the Pomplun Lab engages in rational drug design, developing peptidomimetics and mini- proteins that disrupt cancer-related protein-nucleic acid complexes. Current oncology-focused targets include MYC, Evi1, and Exo1, which are critical in tumour progression and malignancy. By combining innovative screening technologies with rational design, the lab aims to overcome traditional limitations in drug discovery, opening new avenues for cancer therapeutics. 

About Sebastian Pomplun

My Research

Sebastian Pomplun studied Chemistry and Pharmaceutical Technologies at the University Sapienza, in Rome. In his doctoral studies in organic and medicinal chemistry at the Max-Planck-Institute of Psychiatry in Munich (supervised by Prof. Felix Hausch) he developed asymmetric synthesis strategies for caged bicylic inhibitors of the psychiatric risk factor protein FKBP51. The resulting PhD thesis was awarded with Summa cum Laude in 2015. Sebastian then joined the Chemistry R&D department of Roche Diagnostics GmbH in Penzberg, Germany, as a postdoctoral research scientist. He developed novel bioconjugation reagents, cleavable linkers for peptides and functional building blocks for nanopore sequencing strategies. In 2019 Sebastian received a postdoctoral fellowship from the German Research Foundation (DFG) and joined the Pentelute Lab at the Massachusetts Institute of Technology in Cambridge, USA. At MIT he worked on rational and combinatorial strategies for the discovery of biohybrid molecules targeting disease related nucleic acids. In September 2021 Sebastian started as a tenure track assistant professor at the Leiden Academic Centre for Drug Research (LACDR) at Leiden University. His research is funded by LACDR, an ERC Starting Grant, NWO open competition funding and by the Oncode Accelerator program. Since 2024 Sebastian is a junior investigator in the Oncode Institute. https://pomplunlab.com/ 

Awards
  • ERC-StG-2021 SynTra

Key Publications
  1. Sebastian Pomplun, Muhammad Jbara, Carly Schissel, Ann Boija, Susanne Wilson Hawken, Isaac Klein, and Bradley L. Pentelute; Parallel automated flow synthesis of covalent protein complexes that inhibit MYC-driven transcription; ACS Central Science, 2021, 7, 8, 1408–1418 (OPEN ACCESS) https://doi.org/10.1021/acscentsci.1c00663

  2. Sebastian Pomplun, Zachary P. Gates, Genwei Zhang, Anthony J. Quartararo, and Bradley L. Pentelute; Discovery of nucleic acid binding molecules from combinatorial biohybrid nucleobase peptide libraries; JACS, 2020, 2020, 142, 46, 19642–19651, (highlighted as front cover), https://doi.org/10.1021/jacs.0c08964

  3. Sebastian Pomplun, Muhammad Jbara, Anthony J. Quartararo, Genwei Zhang,Joseph Brown, Yen-Chun Lee, Xiyun Ye, Stephanie Hanna and Bradley L. Pentelute; De Novo Discovery of High Affinity Peptide Binders for the SARS-CoV-2 Spike Protein; ACS Central Science, 2021, 7, 1, 156–163; (OPEN ACCESS) https://doi.org/10.1021/acscentsci.0c01309

  4. Sebastian Pomplun*, Mohamed YH Mohamed, Tobias Oelschlaegel, Christian Wellner, Frank Bergmann; Efficient Pictet Spengler Bioconjugation with N-Substituted Pyrrolyl Alanine Derivatives; Angew. Chem. Int. Ed., 2019, 58 (11), 3542; (*corresponding author); https://doi.org/10.1002/anie.201814200

  5. J. Miguel Mata,+  Edith van der Nol,+ and  Sebastian J. Pomplun*; Advances in Ultrahigh Throughput Hit Discovery with Tandem Mass Spectrometry Encoded Libraries; JACS, 2023, (OPEN ACCESS) https://doi.org/10.1021/jacs.3c04899; (+ = equal contribution)

Members

Sebastian Pomplun
Group leader
Athanasios Patsos    
Phd student
Brecht Ellenbroek    
PhD student
Edith van der Nol    
Phd student
Hugo Minnee    
Lab Technician
J. Miguel Mata    
PhD student
Jan Pascal Kahler    
Postdoc
Jingming Liu    
PhD student