SFB 765:  Multivalency as Chemical Organisation and Action Principle: New Architectures, Functions and Applications

• Subject Area: Chemistry ; Biology ; Mathematics ; Medicine ; Physics
• Term: from 2008 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 32049920

• Final Report Year: 2020

Final Report Abstract

Multivalence is a key principle in nature for building strong but reversible chemical interactions between two entities, e.g. receptors and ligands, viruses and cells or between two cell surfaces. Multivalent binding is based on several simultaneous molecular recognition processes, which are mediated either by uniform non-covalent interactions (homomultivalence) or by several different non-covalent interactions (heteromultivalence). Multivalence plays a decisive role, for example, in the self-organization of matter, in catalysis, and in biological systems for recognition, adhesion, and signal processes. Simultaneous multivalent interactions of several ligands form a multivalent ligand system at a corresponding multivalent receptor that can cause significant amplifications of binding constants and thus dramatically enhanced binding on a molecular scale, so that equilibria are shifted completely in favor of the formed complexes. The targeted design of new multivalent molecules is of great importance for important biological questions, e.g. for the inhibition of inflammation and the prevention of viral infections, as well as for the targeted synthesis of functional molecule architectures, surface structures or controlled nanoparticle interactions. The chemical and biological mechanisms and the influence of differently dimensioned scaffold architectures, which underlie these multivalent interactions, have been the central topic of the SFB 765. Trend-setting successes were achieved in the first two funding periods. The experimental and theoretical investigation of bivalent and trivalent binding systems in the gas phase, in solution and on surfaces was successful. In some cases, it was also possible to precisely correlate quantitative data between theory and experiment. The research also showed the importance of size, shape, flexibility and dynamics of the scaffold architecture, especially for the planar interaction with biological systems. The success is illustrated by the development of a multivalent drug candidate with strong anti-inflammatory activity and highly potent pathogen inhibition. In the third funding period of the SFB 765, a further strengthening of the SFB 765 with regard to application-oriented projects was planned in addition to a focus on organic framework architectures of "soft matter". Multivalent pathogen inhibitors were investigated, which was very forward-looking with regard to the current virus pandemic and provided many useful hints for the design of novel virus inhibitors. A deeper understanding of multivalent interactions on all length scales from the nano- to the micrometer range is crucial for answering central questions and new developments in the field of bio- and material sciences. To accomplish this highly complex and long-term task, the interdisciplinary cooperation of natural scientists with different expertise from biochemistry to theory is necessary. Freie Universität Berlin, Humboldt-University, Technical University of Berlin, Leibniz Institute for Molecular Pharmacology, Charité-Universitätsmedizin Berlin, MPI for Colloids and Interfaces, Zuse Institute Berlin and, in the third funding period, the Robert Koch Institute have developed great expertise and strong scientific interactions in the investigation of functional molecular aggregates to answer questions from the life and materials sciences. In the third funding period of the SFB 765, the areas of Pharmaceutical Chemistry and Theoretical Chemistry/Biophysics have been specifically strengthened by the appointments of recent years, in order to deepen the multifaceted and important topic of "Multivalence". The special charm of SFB 765 was the unique interaction of synthetic expertise, physico-chemically and theoretically oriented projects with biologically inspired questions, which led to a new quality of understanding of multivalence and put it on a precise theoretical basis, enabling medical issues such as inflammation, bacterial and viral infections to be more specifically addressed for future applications. Through these precise measurements and modelling, the SFB 765 has also succeeded in further developing a quantitative understanding of the multivalency at biological interfaces, especially of viruses. The precisely fitting interaction of DNA-, polymer- and phage-based scaffold architectures has resulted in the best binding constants, which is also of great importance for future applications of multivalence. With these long-term and extremely interesting research perspectives, the SFB 765 has further expanded its pioneering function in Germany and internationally in the third funding period.

Publications

• Proc Natl Acad Sci USA, 2010, 107, 19679
  Dernedde, Jens; Rausch, Alexandra; Weinhart, Marie; Enders, Sven; Tauber, Rudolf; Licha, Kai; Schirner, Michael; Zügel, Ulrich; von Bonin, Arne & Haag, Rainer
  
• ChemBioChem, 2011, 12, 2587-2598
  Shan, Min; Bujotzek, Alexander; Abendroth, Frank; Wellner, Anja; Gust, Ronald; Seitz, Oliver; Weber, Marcus & Haag, Rainer
  
• Org. Biomol. Chem., 2011, 9, 7448-7456
  Roskamp, Meike; Enders, Sven; Pfrengle, Fabian; Yekta, Shahla; Dekaris, Vjekoslav; Dernedde, Jens; Reissig, Hans-Ulrich & Schlecht, Sabine
  
• Chem. Commun., 2012, 48, 522-524
  Artner, Lukas M.; Merkel, Lars; Bohlke, Nina; Beceren-Braun, Figen; Weise, Christoph; Dernedde, Jens; Budisa, Nediljko & Hackenberger, Christian P. R.
  
• J. Am. Chem. Soc., 2012, 134, 20490-20497
  Schade, Matthias; Knoll, Andrea; Vogel, Alexander; Seitz, Oliver; Liebscher, Jürgen; Huster, Daniel; Herrmann, Andreas & Arbuzova, Anna
  
• PLOS ONE, 2013, 8, e82352
  Majkut, Paul; Claußnitzer, Iris; Merk, Helmut; Freund, Christian; Hackenberger, Christian P. R. & Gerrits, Michael
  
• Adv. Healthc. Mater., 2015, 4, 2154-2162
  Reimann, Sabine; Gröger, Dominic; Kühne, Christian; Riese, Sebastian B.; Dernedde, Jens & Haag, Rainer
  
• Beilstein J. Org. Chem., 2015, 11, 784-791
  Mühlberg, Michaela; Hoesl, Michael G.; Kuehne, Christian; Dernedde, Jens; Budisa, Nediljko & Hackenberger, Christian P. R.
  
• Beilstein J. Org. Chem., 2015, 11, 837-847
  Koschek, Katharina; Durmaz, Vedat; Krylova, Oxana; Wieczorek, Marek; Gupta, Shilpi; Richter, Martin; Bujotzek, Alexander; Fischer, Christina; Haag, Rainer; Freund, Christian; Weber, Marcus & Rademann, Jörg
  
• Biomacromolecules, 2015, 16, 2188-2197
  Zacco, Elsa; Anish, Chakkumkal; Martin, Christopher E.; v. Berlepsch, Hans; Brandenburg, Enrico; Seeberger, Peter H. & Koksch, Beate
  
• ChemBioChem, 2015, 16, 742-745
  Völler, Jan; Biava, Hernan; Koksch, Beate; Hildebrandt, Peter & Budisa, Nediljko
  
• J. Am. Chem. Soc., 2015, 137, 2572-2579
  Vonnemann, Jonathan; Liese, Susanne; Kuehne, Christian; Ludwig, Kai; Dernedde, Jens; Böttcher, Christoph; Netz, Roland R. & Haag, Rainer
  
• Linear polyglycerol derivatives, a method for manufacturing and applications, EP16153144.7A, 2016
  R. Haag, A. Herrmann, S. Bhatia and D. Lauster
  
• Mol. Cell. Proteomics, 2015, 14, 2961
  Kuropka, Benno; Witte, Amelie; Sticht, Jana; Waldt, Natalie; Majkut, Paul; Hackenberger, Christian P.R.; Schraven, Burkhart; Krause, Eberhard; Kliche, Stefanie & Freund, Christian
  
• Nano Lett., 2016, 16, 807-811
  Lai, Chian-Hui; Hütter, Julia; Hsu, Chien-Wei; Tanaka, Hidenori; Varela-Aramburu, Silvia; De Cola, Luisa; Lepenies, Bernd & Seeberger, Peter H.
  
• ACS Nano, 2017, 11, 702-712
  Liese, Susanne; Gensler, Manuel; Krysiak, Stefanie; Schwarzl, Richard; Achazi, Andreas; Paulus, Beate; Hugel, Thorsten; Rabe, Jürgen P. & Netz, Roland R.
  
• Adv. Healthc. Mater., 2016, 5, 2922-2930
  Ziem, Benjamin; Thien, Hendrik; Achazi, Katharina; Yue, Constanze; Stern, Daniel; Silberreis, Kim; Gholami, Mohammad Fardin; Beckert, Fabian; Gröger, Dominic; Mülhaupt, Rolf; Rabe, Jürgen P.; Nitsche, Andreas & Haag, Rainer
  
• Angew. Chem. Int. Ed., 2016, 55, 15510-15514
  Köhling, Sebastian; Exner, Matthias P.; Nojoumi, Saba; Schiller, Jürgen; Budisa, Nediljko & Rademann, Jörg
  
• Bioorthogonale 3d-in situ-hydrogele in Form eines auf einem Träger immobilisierten Netzwerks für Biosensoren sowie Verfahren zu deren Herstellung, Germany Pat., DE102017112012A1, 2016
  R. Haag, L. Kaufmann and U. Schedler
  
• Chem. Eur. J., 2016, 22, 15475-15484
  von Krbek, Larissa K. S.; Achazi, Andreas J.; Solleder, Marthe; Weber, Marcus; Paulus, Beate & Schalley, Christoph A.
  
• Novel furazan-3-carboxylic acid derivatives and use thereof in treatment of cancer. EP16192394, 2016
  J. Rademann, E. L. Wong, C. Arkona, B. G. Kim and E. Nawrotzky
  
• Angew. Chem. Int. Ed., 2017, 56, 5931-5936
  Lauster, Daniel; Glanz, Maria; Bardua, Markus; Ludwig, Kai; Hellmund, Markus; Hoffmann, Ute; Hamann, Alf; Böttcher, Christoph; Haag, Rainer; Hackenberger, Christian P. R. & Herrmann, Andreas
  
• Biomaterials, 2017, 138, 22-34
  Bhatia, Sumati; Lauster, Daniel; Bardua, Markus; Ludwig, Kai; Angioletti-Uberti, Stefano; Popp, Nicole; Hoffmann, Ute; Paulus, Florian; Budt, Matthias; Stadtmüller, Marlena; Wolff, Thorsten; Hamann, Alf; Böttcher, Christoph; Herrmann, Andreas & Haag, Rainer
  
• Chem. Eur. J., 2017, 23, 2877-2883
  von Krbek, Larissa K. S.; Achazi, Andreas J.; Schoder, Stefan; Gaedke, Marius; Biberger, Tobias; Paulus, Beate & Schalley, Christoph A.
  
• Chem. Eur. J., 2017, 23, 2960-2967
  Schröder, Hendrik V.; Hupatz, Henrik; Achazi, Andreas J.; Sobottka, Sebastian; Sarkar, Biprajit; Paulus, Beate & Schalley, Christoph A.
  
• Chem. Soc. Rev., 2017, 46, 2622-2637
  von Krbek, Larissa K. S.; Schalley, Christoph A. & Thordarson, Pall
  
• J. Am. Chem. Soc., 2017, 139, 16389-16397
  Bandlow, Victor; Liese, Susanne; Lauster, Daniel; Ludwig, Kai; Netz, Roland R.; Herrmann, Andreas & Seitz, Oliver
  
• Pentafluorophosphate derivative, its uses and an appropriate manufacturing method. EP 17190937.7, 2017
  J. Rademann, S. Wagner and M. Accorsi
  
• Angew. Chem. Int. Ed., 2018, 57, 14121-14124
  von Krbek, Larissa K. S.; Roberts, Derrick A.; Pilgrim, Ben S.; Schalley, Christoph A. & Nitschke, Jonathan R.
  
• Coating compound and coating arrangement. Deutschland Pat., EP3263623A1, 2018
  R. Haag, M. Weinhart, Q. Wei and L. Yu
  
• Nanoscale, 2018, 10, 21425-21433
  Schröder, Hendrik V.; Mekic, Amel; Hupatz, Henrik; Sobottka, Sebastian; Witte, Felix; Urner, Leonhard H.; Gaedke, Marius; Pagel, Kevin; Sarkar, Biprajit; Paulus, Beate & Schalley, Christoph A.
  
• Small, 2018, 14, 1800189
  Donskyi, Ievgen; Drüke, Moritz; Silberreis, Kim; Lauster, Daniel; Ludwig, Kai; Kühne, Christian; Unger, Wolfgang; Böttcher, Christoph; Herrmann, Andreas; Dernedde, Jens; Adeli, Mohsen & Haag, Rainer
  
• Angew. Chem. Int. Ed., 2019, 58, 3496-3500
  Schröder, Hendrik V.; Stein, Felix; Wollschläger, Jan M.; Sobottka, Sebastian; Gaedke, Marius; Sarkar, Biprajit & Schalley, Christoph A.
  
• Biophys. J., 2019, 116, 1037-1048
  Reiter-Scherer, Valentin; Cuellar-Camacho, Jose Luis; Bhatia, Sumati; Haag, Rainer; Herrmann, Andreas; Lauster, Daniel & Rabe, Jürgen P.
  
• Computation, 2019, 7
  Erlekam, Franziska; Igde, Sinaida; Röblitz, Susanna; Hartmann, Laura & Weber, Marcus
  
• Nano Letters, 2019, 19, 1875-1882
  Müller, Matthias; Lauster, Daniel; Wildenauer, Helen H. K.; Herrmann, Andreas & Block, Stephan
  
• Small, 2019, 15, 1805430
  Guday, Guy; Donskyi, Ievgen S.; Gholami, Mohammad Fardin; Algara‐Siller, Gerardo; Witte, Felix; Lippitz, Andreas; Unger, Wolfgang E. S.; Paulus, Beate; Rabe, Jürgen P.; Adeli, Mohsen & Haag, Rainer
  
• Angew. Chem. Int. Ed., 2020
  Achazi, Katharina; Haag, Rainer; Ballauff, Matthias; Dernedde, Jens; Kizhakkedathu, Jayachandran N.; Maysinger, Dusica & Multhaup, Gerd
  
• Angew. Chem. Int. Ed., 2020
  Bachem, Gunnar; Wamhoff, Eike‐Christian; Silberreis, Kim; Kim, Dongyoon; Baukmann, Hannes; Fuchsberger, Felix; Dernedde, Jens; Rademacher, Christoph & Seitz, Oliver
  
• Angew. Chem. Int. Ed., 2020, 59, 12417-12422
  Bhatia, Sumati; Hilsch, Malte; Cuellar‐Camacho, Jose Luis; Ludwig, Kai; Nie, Chuanxiong; Parshad, Badri; Wallert, Matthias; Block, Stephan; Lauster, Daniel; Böttcher, Christoph; Herrmann, Andreas & Haag, Rainer
  
• Angew. Chem. Int. Ed., 2020, 59, 8776-8785
  Mikolajczak, Dorian J.; Berger, Allison A. & Koksch, Beate
  
• J. Am. Chem. Soc., 2020, 142, 12181-12192
  Cuellar-Camacho, Jose Luis; Bhatia, Sumati; Reiter-Scherer, Valentin; Lauster, Daniel; Liese, Susanne; Rabe, Jürgen P.; Herrmann, Andreas & Haag, Rainer
  
• Langmuir, 2020, 36, 4827-4834
  Schmudde, Madlen; Grunewald, Christian; Risse, Thomas & Graf, Christina
  
• Nano Lett., 2020, 20, 5367-5375
  Nie, Chuanxiong; Stadtmüller, Marlena; Yang, Hua; Xia, Yi; Wolff, Thorsten; Cheng, Chong & Haag, Rainer
  
• Nat. Nanotechnol., 2020, 15, 373–379
  Lauster, Daniel; Klenk, Simon; Ludwig, Kai; Nojoumi, Saba; Behren, Sandra; Adam, Lutz; Stadtmüller, Marlena; Saenger, Sandra; Zimmler, Stephanie; Hönzke, Katja; Yao, Ling; Hoffmann, Ute; Bardua, Markus; Hamann, Alf; Witzenrath, Martin; Sander, Leif E.; Wolff, Thorsten; Hocke, Andreas C.; Hippenstiel, Stefan; ... & Hackenberger, Christian P. R.