Research Field 3

Deike, S., et al. Bioorganic Chemistry 2020, 101, 104012, https://doi.org/10.1016/j.bioorg.2020.104012

Aggregation of amyloid peptides results in severe neurodegenerative diseases. We here report the preparation of beta-turn mimetic conjugates containing synthetic turn mimetic structures in the turn region of Aβ₄₀ and Aβ_16-35, replacing 2 amino acids in the turn-region G₂₅ – K₂₈. The structure of the turn mimic induces both, acceleration of fibrillation and the complete inhibition of fibrillation, confirming the importance of the turn region on the aggregation. Reproduced with permission. Copyright 2020© Elsevier B. V.

Kumar, S., et al. Macromolecular Bioscience 2020,2000048,DOI: https://doi.org/10.1002/mabi.202000048.

The synthesis and self-assembly of peptide-polymer conjugates into fibrillar nanostructures are reported, based on the amyloidogenic peptide KLVFF. A strategy for rational synthesis of polymer?peptide conjugates is documented via tethering of the amyloidogenic peptide segment LVFF (Aβ_17-20) and its modified derivative FFFF to the hydrophilic poly(ethylene glycol) monomethyl ether (mPEG) polymer via thio-bromo based “click” chemistry. The peptide-guided self-assembling behavior of the amphiphilic supramolecular materials is investigated exhibiting fibrillar nanostructure formation in binary aqueous solution mixture. Reproduced with permission. Copyright 2020©, WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Freudenberg, J., et al. ACS Macro Letters 2020, 686-692, https://doi.org/10.1021/acsmacrolett.0c00218.

2-Aminoisobutyric acid (Aib) is an essential amino acid, leading to the formation of peptAibols as microbiologically active peptides and proteins. We here report on the ring-opening polymerization (ROP) of Aib-NCA (N-carboxy-anhydrides), enabling to prepare distinct Aib-polymers up to molecular weights of 1400 g/mol with precise end-group control. The attachment of chiral (D or L)-amino acids allows to systematically investigate the helical screw-sense of poly(Aib)n, resulting in chiral induction to form either left (M)- or right (P)-handed screw-senses. The approach is extended toward a switchable, chiral azo-headgroup, able to change chirality of the attached poly(Aib)n via a light-induced trigger. Reproduced with permission. Copyright 2020©, American Chemical Society.

Canalp, M., et al. RSC Advances 2020,10 (3), 1287-1295,DOI: http://dx.doi.org/10.1039/C9RA09189K.

Hybrid polymers of peptides resembling (partially) folded protein structures are promising materials in biomedicine, especially in view of folding-interactions between different segments. In this study polymers bearing repetitive peptidic folding elements, composed of N-terminus functionalized bis-ω-ene-functional oligo-l-lysine(carboxybenzyl(Z))s (Lysn) with repeating units (n) of 3, 6, 12, 24 and 30 were successfully synthesized to study their secondary structure introduced by conformational interactions between their chains. We can demonstrate the influence of chain length of the generated polymers on the formation of secondary structures by comparing Lysnswith varying n values to the ADMET-polymers in a helicogenic solvent. Reproduced by permission of The Royal Society of Chemistry.

Funtan, S., et al. Biomimetics 2019,4 (1), 24,DOI: https://doi.org/10.3390/biomimetics4010024

With the class of shock-absorbing proteins, nature created some of the most robust materials combining both mechanical strength and elasticity.  Here, we report on the synthesis of two different latent mechanophoric copper(I) bis(N-heterocyclic carbene) complexes bearing either two carboxyl groups or two amino groups which allow conjugation reactions with either the N- or the C-terminus of amino acids or peptides. Mechanochemical activation by ultrasound showed conversions in the copper(I)-catalyzed alkyne-azide “click” reaction (CuAAC) up to 9.9% proving the potential application for the time and spatial controlled CuAAC.

Freudenberg, J., et al. Macromolecules 2019,52 (12), 4534-4544,DOI: https://doi.org/10.1021/acs.macromol.9b00684.

The synthesis of multisegmented polymers containing repetitive oligo-(^BnAsp_n, ^BnGlu_n) sequences separated by methylene units and their secondary structure formation in solution and in the solid state are reported. Combining ring-opening polymerization (ROP) of N-carboxyanhydrides with postfunctionalization of the respective N-terminus yields the oligo-( ^BnAsp₃, ^BnAsp₁₀, ^BnGlu₃, and ^BnGlu₁₀) sequences bearing terminal vinyl groups on either side of the polymer chain by preparative gel permeation chromatography generate polymers of a precise degree of polymerization (n = 3, 10; m = 1–136). β-sheet conformation is identified as the thermodynamically more stable conformation, as supported by our experiments in the solid state and in solution. Reproduced with permission. Copyright 2019©, American Chemical Society.

Evgrafova, Z., et al. Physical Chemistry Chemical Physics 2019,21 (37), 20999-21006,DOI: http://dx.doi.org/10.1039/C9CP02683E.

A substantial number of diseases leading to loss of neurologic functions such as Morbus Alzheimer, Morbus Parkinson, or Chorea Huntington are related to the fibrillation of particular amyloidogenic peptides. We investigated amyloid-beta 1–40 peptide (Aβ_1–40) fibrillation in mixture with thermoresponsive poly(oligo(ethylene glycol)macrylates), in which the polymer’s hydrophobicity is tuned by variation of the number of ethylene glycol-units in the side chain (m = 1–9), the end groups (B = butoxy; C = carboxy; D = dodecyl; P = pyridyldisulfide). The polymers were prepared via RAFT-polymerization. Less hydrophilic polymers (m = 1–2) were able to both decrease and elongate the lag (tlag) and characteristic times (tchar) of Aβ_1–40 fibril formation in dependence of their end groups, molecular mass and hydrophilicity. Reproduced with permission from the PCCP Owner Societies.

Evgrafova, Z., et al. ChemPhysChem2019,20 (2), 236-240,DOI: https://doi.org/10.1002/cphc.201800867.

Covalent conjugates between a synthetic polymer and a peptide hormone were used to probe the molecular extension of these macromolecules. NMR spectroscopy of ¹⁵N labeled parathyroid hormone (PTH) was employed to visualize the shroud-like polymer conformation of the conjugated chimeras. Reproduced by permission. Copyright © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Canalp, M., et al. RCS Advances2019,9 (38), 21707-21714,DOI: http://dx.doi.org/10.1039/C9RA03099A.

Narrow-dispersed, end group-telechelic, oligomeric-(l-lysine(carboxybenzyl (Z)/trifluoroacetyl (TFA)))ns (n = 3–33) were prepared as a model system for studying assembly and secondary structure formation. Fibril formation of oligomeric-(L-lysine(Z/TFA))_ns with shorter chain lengths (n = 7 and n = 3) were chosen to investigate the effect of the number of repeating units’ role on the self-assembly of the oligomers in TFE. Reproduced by permission of The Royal Society of Chemistry.

Deike, S., et al. Macromolecules 2017,50 (7), 2637-2644,DOI: http://dx.doi.org/10.1021/acs.macromol.7b00343.

Chiral and achiral β-turn mimetic polymer conjugates were synthesized, based on chiral helical poly(n-hexyl isocyanate)s (PHICs), and allowing to tune the distance between the PHIC-helix and the chiral center from 7 to 14 Å.. Circular dichroism (CD) spectra confirmed chirality induction from the chiral β-turn mimetic structure to the polymer backbone of the achiral PHIC over five chemical bonds via postpolymerization modification, and revealed a distance-dependent effect for the transmission of stereochemical information. Reproduced with permission. Copyright 2017©, American Chemical Society.