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

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

DFG Programme Collaborative Research Centres

Completed projects

Applicant Institution Freie Universität Berlin
Participating University Humboldt-Universität zu Berlin; Technische Universität Berlin
Participating Institution Charité - Universitätsmedizin Berlin; Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP)
im Forschungsverbund Berlin e.V.; Max-Planck-Institut für Kolloid- und Grenzflächenforschung
Wissenschaftspark Potsdam-Golm; Robert Koch-Institut (RKI); Zuse-Institut Berlin (ZIB)
Spokesperson Professor Dr. Rainer Haag