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/rigidity.2, 3 They allow to study refolding and cooperative phenomena, similar to protein folding and amyloid assembly.4-7 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,8 assembly with embedded constrained folding elements,2 and dynamic secondary structure-elements (such as beta-folds, alpha-helices)4, 6 were successfully introduced into the polymer chains, acting as biomimetics for larger proteins.4-7 Currently, the concept is extended onto polymer/amyloid-molecules to design, understand and influence the folding and aggregation pathways of new such detrimentally aggregating proteins.9, 10

Reproduced with permission from the reference.12 Copyright 2017©, American Chemical Society.
Reproduced with permission from the reference13. 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,11, 12 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 moiety.13 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. Recent work describes the effects of various head-groups together with an expansion towards induction of chirality in the solid state and the use of chiral induction in transistors.14


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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: 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:
  3. Reimann, S., et al., Synthesis and Crystallization of Precision Polymers with Repetitive Folding Elements. Macromolecular Chemistry and Physics 2014, 215 (20), 1963-1972, DOI:
  4. 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:
  5. Freudenberg, J., et al., Multisegmented Hybrid Polymer Based on Oligo-Amino Acids: Synthesis and Secondary Structure in Solution and in the Solid State. Macromolecules 2019, 52 (12), 4534-4544, DOI:
  6. 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:
  7. Freudenberg, J., et al., Precision polymers containing main-chain-amino acids: ADMET polymerization and crystallization. RSC Advances 2017, 7 (75), 47507-47519, DOI:
  8. Appiah, C., et al., Crystallization behavior of precision polymers containing azobenzene defects. European Polymer Journal 2017, 97 (Supplement C), 299-307, DOI: 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: Appiah, C., et al., Synthesis and characterization of new photoswitchable azobenzene-containing poly(?-caprolactones). RSC Advances 2016, 6 (8), 6358-6367, DOI:
  9. Evgrafova, Z., et al., Modulation of amyloid β peptide aggregation by hydrophilic polymers. Physical Chemistry Chemical Physics 2019, 21 (37), 20999-21006, DOI: Funtan, S., et al., Amyloid beta aggregation in the presence of temperature-sensitive polymers. Polymers MDPI 2016, 8 (5), 178, DOI: Paschold, A., et al., Modulating the Fibrillization of Parathyroid-Hormone (PTH) Peptides: Azo-Switches as Reversible and Catalytic Entities. Biomedicines 2022, 10 (7), 1512 ,DOI: . Sen, N., et al., Membrane Anchored Polymers Modulate Amyloid Fibrillation. Macromolecular Rapid Communications 2021, 42 (12), 2100120, DOI: Kumar, S., et al., Bifunctional Peptide–Polymer Conjugate-Based Fibers via a One-Pot Tandem Disulfide Reduction Coupled to a Thio-Bromo “Click” Reaction. ACS Omega 2020, 5 (30), 19020-19028, DOI: Kumar, S., et al., Thio-Bromo “Click” Reaction Derived Polymer–Peptide Conjugates for Their Self-Assembled Fibrillar Nanostructures. Macromolecular Bioscience 2020, 20 (6), 2000048, DOI: Kumar, S., et al., Peptide-induced RAFT polymerization via an amyloid-β17–20-based chain transfer agent. Soft Matter 2020, 16 (30), 6964- 6968, DOI: Deike, S., et al., β-Turn mimetic synthetic peptides as amyloid-β aggregation inhibitors. Bioorganic Chemistry 2020, 101, 104012, DOI:
  10. Evgrafova, Z., et al., Probing Polymer Chain Conformation and Fibril Formation of Peptide Conjugates. ChemPhysChem 2019, 20 (2), 236-240, DOI:
  11. Deike, S., et al., Constraining Polymers into β-Turns: Miscibility and Phase Segregation Effects in Lipid Monolayers. Polymers 2017, 9 (8), 369, DOI:
  12. Deike, S., et al., Induction of Chirality in β-Turn Mimetic Polymer Conjugates via Postpolymerization “Click” Coupling. Macromolecules 2017, 50 (7), 2637-2644, DOI:
  13. 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:
  14. Rohmer, M., et al., Chiral amines as initiators for ROP and their chiral induction on poly(2-aminoisobutyric acid) chains. Polymer Chemistry 2021, 12 (43), 6252- 6262, DOI: