Bruno Voigt, Zhanna Evgrafova, Monika Baumann, Madlen Stephani, Marvin Umlandt, Wolfgang H. Binder, Jochen Balbach
Faculty of Natural Sciences II, Martin-Luther-Universität Halle-Wittenberg, D-06120 Halle, Germany
The parathyroid hormone (PTH) is an 84 residue peptide from the parathyroid glands which controls 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. Amyloidogenic properties of PTH have been reported [1]. Here we show the in vitro formation of amyloid fibrils of PTH 1-84 and of the pharmaceutically relevant N-terminal fragment PTH 1-34 under physiological conditions. To get further insights into the mechanism of amyloid fibrillation we investigated the effect of thermoresponsive polymers [2] on PTH. We covalently attached polyacrylate based polymers to 15N isotope labelled PTH 1-84 and used two dimensional NMR techniques for the characterization of the resulting chimaeras. This allows the observation of amino acid sequence specific changes of the cross peaks corresponding to the peptide backbone according to the polymer state. The studies revealed strong dependencies of chemical shifts on the temperature, the peptide attachment site and the polymer molecular weight.
References
[1] Gopalswamy, M.; Kumar, A.; Adler, J.; Baumann, M.; Henze, M.; Kumar, S.T.; Fändrich, M.; Scheidt, H.A.; Huster, D.; Balbach, J., Biochim Biophys Acta 2015, 1854, 249-257. (link)
[2] Funtan, S.; Evgrafova, Z.; Adler, J.; Huster, D.; Binder, W.H., Polymers 2016, 8, 178. (link)