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Technical University of Munich

Next Generation Drug Design

The goal of the TUM Innovation Network Next Generation Drug Design (NextGenDrugs) is to act as a pioneer for completely new approaches in drug development. In particular in the field of cancer medicine, but also in infectious diseases, such approaches are urgently needed and are now accessible due to recent developments in the life sciences. NextGenDrugs brings together experts from medicine, life sciences, chemistry and computational sciences to jointly realize this goal.

Within NextGenDrugs, we will spearhead the development of drugs with a new mode of action: Can we specifically modulate cellular protein-networks to kill cancer cells? In parallel, we will develop completely new classes of biomolecules as targets for cancer therapy. In order to fight cancer cells while sparing the body's own cells, another focus of NextGenDrugs is to increase the targeting specificity of drugs. In addition to new approaches in cancer therapy, there is an urgent need for action in the field of infectious diseases. For the first time, we will intervene in the communication of bacteria with their host to circumvent resistances arising from classical therapies.

Our Team

Associated partner: 

Doctoral researchers

  • E Lei (Organic Chemistry II)
  • Jonathan Held (Cellular Protein Biochemistry)
  • Alexander Belka (Molecular Oncology and Functional Genomics)
  • Agnieszska Gaska (ITranslational Microbiome Data Integration, Institute for Food & Health - ZIEL)
  • Antje Gabriel (Internal Medicine III, Hematology and Oncology)
  • Ruiming He (Biotechnology)
  • Niklas Dold (Biomolecular NMR-Spectroscopy)

Postdoctoral researchers

  • Dr. Priska Auf der Maur (Internal Medicine III, Hematology and Oncology)
  • Dr. Carolin Kitzberger (Imaging and Biomarkers in Oncology)
  • Dr. Jack O'Shea (Protein Chemistry)
  • Dr. Ibrahim Mohd (Biomolecular Dynamics)

Other involved researchers

  • M.Sc. Yassmine El Harraoui (Organic Chemistry II)
  • M.Sc. Markus Schwarz (Organic Chemistry II)
  • Dr. Shu-Yu Shen (Biomolecular Dynamics)
  • Dr. Isabel Aschenbrenner (Cellular Protein Biochemistry)
  • Prof. Manuel Kaulich (Institute of Biochemistry II - Goethe University Frankfurt)
  • M.Sc. Jacob Stroh (Internal Medicine III, Hematology and Oncology)
  • M.Sc. Tisya Banergee (Biotechnology)
  • Dr. Santiago Martinez-Lumbreras (Biomolecular NMR-Spectroscopy)

Doctoral theses

  • Targets of brain natriuretic peptides in bacteria (E. Lei)
  • Cytokines in interkingdom signaling (Jonathan Held)
  • Genome-scale screening for coding and non-coding RNAs in cancer (Alexander Belker)
  • Interkingdom signaling molecules (Agnieszka Gaska)
  • Role of the UPS in AML (Antje Gabriel)
  • The role of the the E3 ligase CHIP in cancer biology (Ruiming He)
  • RNA recognition during early spliceosome assembly and modulation by small molecules (Niklas Dold)

Publications

  1. Abdel-Rahman, B. L., Santini, B. L., Calvo-Barreiro, et al. (2024). Design of cyclic peptides as novel inhibitors of ICOS/ICOSL interaction. Bioorganic & Medicinal Chemistry Letters, 99, 129599. https://doi.org/10.1016/j.bmcl.2024.129599
  2. Montero, J.J., Trozzo, R., Sugden, M. et al. Genome-scale pan-cancer interrogation of lncRNA dependencies using CasRx. Nat Methods 21, 584–596 (2024). https://doi.org/10.1038/s41592-024-02190-0
  3. Chen, S. Y., & Zacharias, M. (2023). What makes a good protein−protein interaction stabilizer: Analysis and application of the dual-binding mechanism. ACS Central Science, 9(5), 969-979. https://doi.org/10.1021/acscentsci.3c00003
  4. Santini, B. L., & Zacharias, M. (2022). Rapid Rational Design of Cyclic Peptides Mimicking Protein-Protein Interfaces. Methods in molecular biology (Clifton, N.J.), 2405, 231–244. https://doi.org/10.1007/978-1-0716-1855-4_12
  5. Montero, J. J., Trozzo, R., Sugden, M., et al. (2024). Genome-scale pan-cancer interrogation of lncRNA dependencies using CasRx. Nature Methods, 21(584–596). https://doi.org/10.1038/s41592-024-02190-0
  6. Aschenbrenner, I., Böckler, M., Franke, F., Liebl, K., Catici, D. A. M., Brandl, M., Behnke, J., & Feige, M. J. (2024). Development of an enabling platform biotechnology for the production of proteins. Biological chemistry, 405(7-8), 471–483. https://doi.org/10.1515/hsz-2023-0376
  7. Chen, S. Y., Koch, M., Chávez-Gutiérrez, L., & Zacharias, M. (2023). How Modulator Binding at the Amyloidβ-γ-Secretase Interface Enhances Substrate Binding and Attenuates Membrane Distortion. Journal of medicinal chemistry, 66(24), 16772–16782. https://doi.org/10.1021/acs.jmedchem.3c01480
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