Doctoral students seminar (August 7, 2018)

Location: 
Martin-Luther-Universität Halle-Wittenberg 
Von-Danckelmann-Platz 3, SR 1.04
06120 Halle (Saale) 

Time: 3.30pm - 5.00pm 

Link to Google-Maps

The parathyroid hormone (PTH) is an 84 residue peptide produced by the para-thyroid glands controlling the calcium and phosphate level in human blood. The peptide adopts an α-helical conformation at the N-terminus and is intrinsically disordered at the C-terminus [1]. In this talk the formation of amyloid fibrils of the full-length PTH 1-84 as well as of the biologically active fragment PTH 1-34 will be reported.

To get further insights into the mechanism of amyloid fibrillation we investigated the effect of thermoresponsive polymers on PTH [2]. We covalently attached polyacrylate based polymers to ¹⁵N isotope labelled PTH 1-84 and employed two dimensional NMR spectroscopy techniques for the characterization of the resulting chimaeras. This allows the visualization of amino acid specific changes of the peptide backbone according to the conformation of the conjugated polymer. The studies revealed strong dependencies of chemical shifts on the temperature, the peptide attachment site and the polymer molecular weight. However, conjugated PTH is still able to form amyloid fibrils though it shows altered aggregation kinetics.

Side-chain architecture offers the attractive possibility to create a variety of semiconducting polymers by attaching different active molecules to a polymeric backbone. While this approach opens a large field of chemical modifications, only little is known about the packing behavior of the active side-chains and the influence of the backbone on the ordering in these systems. We here present a study of the interplay between crystallization and backbone molecular dynamics in two side-chain polymers. A polystyrene (PS) backbone was grafted with two different pendant perylene bisimides (PBIs) carrying either a hydrophobic alkyl (PBI1) or a hydrophilic oligo ethylene glycol swallow tail (PBI2) as solubilizing end group. In order to study the effect of the morphological confinement of a backbone on side-chain crystallization, the low molecular weight PBIs and the polymers were compared using temperature dependent small- and wide-angle x-ray scattering (SAXS/WAXS), grazing incidence wide angle x-ray scattering (GIWAXS) and differential scanning calorimetry (DSC) as central methods. The ordering of the side-chain polymers was found to strongly depend on the interplay with the molecular dynamics of the backbone. While the small molecule PBIs adopt a liquid crystalline order, the liquid crystalline ordering is hindered in the case of the PBI1 carrying polymer and even suppressed in the case of the PBI2 carrying polymer. Both, the glass transition temperature of the backbone, as well as the ordering temperatures of the PBIs were found to increase due to the morphological constrain of the grafting. The stronger increase of the backbone glass transition temperature shifts it into the vicinity of the liquid crystalline ordering temperature of the PBIs. As a result, the ordering is hindered in the case of the PBI1 carrying polymer and even suppressed in the case of the PBI2 carrying polymer. Nevertheless, in the absence of lateral ordering a strong tendency of PBI aggregation accompanied with π-stacking was found in the PBI2 carrying polymer possibly explaining the relatively high electron mobility of these disordered materials. In conclusion, the coupling of the molecular dynamics of the backbone and the side-chains are identified as a new design parameter, which has a drastic effect on ordering and crystallization of side-chain polymers.