SFB 1093:  Supramolecular Chemistry on Proteins

• Subject Area: Chemistry ; Biology ; Medicine
• Term: from 2014 to 2022
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 229838028

The CRC aims at applying recent knowledge and methods from supramolecular chemistry to achieve specific interaction with proteins by artificial ligands. In contrast to classic medicinal chemistry, the supramolecular ligands will not only be bound to well-defined clefts, but also on the protein surface, in shallow grooves or in pores. To this end, various new concepts are explored by the chemists, who design and synthesize supramolecular ligands, characterize their binding profile and pass them on to the biologists. Here, the new ligands are employed to answer general biological questions, which can best be tackled with supramolecular chemistry. Inter alia, specific protein recognition by synthetic ligands helps to elucidate biochemical mechanisms of allosteric and cooperative protein activation, or the function of protein pores. Specific inhibition or reinforcement of protein protein interactions will clarify their biological function, e.g. in chaperones, proteases, transport systems and mitotic regulators. Through the unique combination of novel concepts for protein recognition by artificial ligands with molecular and cell biology, and the strong support from bioinformatics and structural biology we hope to significantly advance the young research field of biosupramolecular chemistry. In the first funding period, we established a proof-of-principle for the CRC concept: various supramolecular ligands (and hosts) were developed for the proteins of our consortium, and shown to bind to protein surfaces and modulate protein function. Invaluable structural information on the preferred complexation site was provided by X-ray crystallography and NMR as well as Raman spectroscopy.In the next funding period, we will significantly advance our supramolecular ligands and send them to larger protein contact areas responsible for natural protein protein interactions. The consortium will also place more emphasis on the modulation of protein functions and subsequent transition to cell culture experiments, with a long-term perspective of potential medical applications.

• DFG Programme: Collaborative Research Centres
• International Connection: Netherlands

Completed projects

• A01 - Protein-recognition by supramolecular ligands from focused combinatorial libraries (Project Heads Schmuck, Carsten ;  Schrader, Thomas ;  Voskuhl, Jens )
• A02 - Chemical tools from protein class-specific supramolecular ligands (Project Head Kaiser, Markus )
• A03 - Designed copolymers and molecular tweezers for protein surface recognition (Project Head Schrader, Thomas )
• A05 - Ultra-small nanoparticles for protein-specific targeting (Project Head Epple, Matthias )
• A06 - DNA origami nanoarchitectures for predesigned spatial confinement of proteins (Project Head Saccà, Barbara )
• A07 - Computational design of supramolecular ligands for specific tweaking of protein interactions (Project Head Hoffmann, Ph.D., Daniel )
• A08 - Exploring protein-recognition by supramolecular binders with MD and QM/MM methods (Project Head Sanchez Garcia, Elsa )
• A09 - Raman spectroscopic monitoring of protein recognition by supramolecular ligands (Project Head Schlücker, Sebastian )
• A10 - Novel luminophors with aggregation induced emission properties for protein recognition (Project Head Voskuhl, Jens )
• A11 - Precision macromolecules for the sequence-controlled presentation of supramolecular ligands (Project Head Hartmann, Laura )
• B01 - Supramolecular ligands modulate assembly and function of HtrA proteases (Project Head Ehrmann, Michael )
• B02 - Probing mechanisms of the Cdc48/p97 segregase with supramolecular ligands (Project Head Meyer, Hemmo )
• B03 - Supramolecular specific inhibitors of intestinal proteases against ischemia/reperfusion in-jury (Project Heads de Groot, Herbert ;  Kirsch, Michael )
• B04 - Modulation of 14-3-3 protein-protein interactions by supramolecular chemistry (Project Head Ottmann, Christian )
• B05 - Rational targeting of intracellular protein transport signals by supramolecular ligands (Project Head Knauer, Ph.D., Shirley )
• B06 - Targeting centromere recruitment of mitotic regulators by supramolecular ligands (Project Head Musacchio, Andrea )
• B07 - Manipulation of the kinetochore-microtubule interface by supramolecular ligands (Project Head Westermann, Stefan )
• MGK - Integrated Research Training Group (Project Heads Epple, Matthias ;  Knauer, Ph.D., Shirley ;  Schmuck, Carsten )
• Z01 - Central Tasks of the CRC (Project Head Schrader, Thomas )
• Z02 - X-ray Crystallography (Project Head Vetter, Ingrid )
• Z03 - NMR Spectroscopy (Project Head Bayer, Peter )

• Applicant Institution: Universität Duisburg-Essen
• Participating Institution: Max-Planck-Institut für molekulare Physiologie
• Participating University: Heinrich-Heine-Universität Düsseldorf; Mathematisch-Naturwissenschaftliche Fakultät
• Spokesperson: Professor Dr. Thomas Schrader