Research Field III

Study biological folding-, assembly and chirality transfer-principles

Secondary-structure of proteins and peptides is crucial for their function in living systems, in its undesired assembly being responsible for e. g. Alzheimer’s or Parkinsons’ disease.1 Within the DFG-funded collaborative research project SFB TRR 102 two projects deal with amyloid-proteins to understand and prevent disease-relevant aggregation via synthetic polymers, able to fold- and unfold during aggregation. Main aim is to understand, control, and inhibit fibrillation by concepts of polymer-science and a deeper understanding of the fibrillation processes. Concepts of synthetic chemistry are combined with proteins to generate hybrid-systems, able to fold and aggregate similar to the native peptide systems. Both, peptide- and polymer chemistry are researched in this area.

Synthesis via ring-opening (ROP) and ADMET-polymerization generates precision-hybrid-polymers consisting of polyamino-acids and repetitive middle segments displaying a defined flexibility/rigidity2-4. They allow to study refolding and cooperative phenomena, similar to protein folding and amyloid assembly.5-8 Recent activities are directed to understand the influence of distance, endgroups and numbers of the folding elements on the final three-dimensional structure of the assemblies. Photoswitchability,9-11 assembly with embedded constrained folding elements,2-3 and dynamic secondary structure-elements (such as beta-folds, alpha-helices)5, 7 were successfully introduced into the polymer chains, acting as biomimetics for larger proteins5-8. Currently, the concept is extended onto polymer/amyloid-molecules to design, understand and influence the folding and aggregation pathways of new such detrimentally aggregating proteins12-14.

Reproduced with permission from the reference.16 Copyright 2017©, American Chemical Society.
Reproduced with permission from the reference17. Copyright 2020©, American Chemical Society.

Chirality is among the chemical principles required for life. We generate  molecules with switchable chirality, where the transfer of chirality onto nonchiral side-chains is probed. As probed in helically chiral polymers,15-16 the transfer of only one chiral group can have influence on many tens of monomers, linked into a polymer chain to yield either right- or left-handed helices, induced just by one chiral moiety17. We employ precisely engineered polymers based on achiral polyisocyanides, polyisocyanates and achiral polyaminoacids to study the influence of a singular chiral-element embedded in the polymer chain. It demonstrates that only one single chiral moiety can display large chirality-transfer-effects, also termed chiral amplification, taken place presumptively in the early times of the universe.


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  2. Danke, V., et al., Structure formation in nanophase-separated systems with lamellar morphology: Comb-like vs. linear precision polymers. European Polymer Journal 2018, 103, 116-123,DOI:
  3. Reimann, S., et al., Synthesis of supramolecular precision polymers: Crystallization under conformational constraints. Journal of Polymer Science Part A: Polymer Chemistry 2017, 55 (22), 3736-3748,DOI:
  4. Reimann, S., et al., Synthesis and Crystallization of Precision Polymers with Repetitive Folding Elements. Macromolecular Chemistry and Physics 2014, 215 (20), 1963-1972,DOI:
  5. Canalp, M. B., et al., Hybrid polymers bearing oligo-l-lysine(carboxybenzyl)s: synthesis and investigations of secondary structure. RSC Advances 2020, 10 (3), 1287-1295,DOI:
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  7. Canalp, M. B., et al., Secondary structure of end group functionalized oligomeric-l-lysines: investigations of solvent and structure dependent helicity. RSC Advances 2019, 9 (38), 21707-21714,DOI:
  8. Freudenberg, J., et al., Precision polymers containing main-chain-amino acids: ADMET polymerization and crystallization. RSC Advances 2017, 7 (75), 47507-47519,DOI:
  9. Appiah, C., et al., Crystallization behavior of precision polymers containing azobenzene defects. European Polymer Journal 2017, 97 (Supplement C), 299-307,DOI:
  10. Appiah, C., et al., Synthesis of photoresponsive main-chain oligomers with azobenzene moieties via ADMET oligomerization and their micellization properties. Polymer Chemistry 2017, 8 (18), 2752-2763,DOI:
  11. Appiah, C., et al., Synthesis and characterization of new photoswitchable azobenzene-containing poly(?-caprolactones). RSC Advances 2016, 6 (8), 6358-6367,DOI:
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  17. Freudenberg, J., et al., Chirality Control of Screw-Sense in Aib-Polymers: Synthesis and Helicity of Amino Acid Functionalized Polymers. ACS Macro Letters 2020, 686-692,DOI: