Dr. rer. nat., Physical Biology, Heinrich Heine University Düsseldorf, Germany, 2015
Diploma, Pharmacy, University Greifswald, Germany, 2010
Association and aggregation play an important role in development of pharmaceutical peptide formulations. A detailed understanding about solvent dependent changes in the association state is an essential tool. These information are relevant for development of stable storage formulations or predictions of the peptide behavior after patient treatment. To analyze peptide association and peptide interactions we combine several hydrodynamic and spectroscopic methods, e.g. static (SLS) and dynamic (DLS) light scattering, circular dichroism spectroscopy and fluorescence spectroscopy.
For example in SLS and DLS experiments we analyze the scattering of laser light by peptide solutions. The mean scattering intensity of the peptide solutions relative to a scattering standard solution is used to determine the molecular mass of the peptide in solution (SLS). In contrast, from the time dependent fluctuation of the scattering signal the diffusion coefficient of the peptide can be calculated (DLS). Combining both methods changes in the peptide association state can be analyzed, e.g. during aggregation.
Wolff M, Schüler A, Gast K, Seckler R, Evers A, Pfeiffer-Marek S, Kurz M, Nagel N, Haack T, Wagner M, Thalhammer A. Self-assembly of Exendin-4-derived dual peptide agonists is mediated by acylation and correlated to the length of conjugated fatty acyl chains. Mol Pharm. 2020, DOI: 10.1021/acs.molpharmaceut.9b01195
Mota C, Esmaeeli M, Coelho C, Santos-Silva T, Wolff M, Foti A, Leimkuhler, S., Romao, M. J. Human aldehyde oxidase (hAOX1): structure determination of the Moco-free form of the natural variant G1269R and biophysical studies of single nucleotide polymorphisms. FEBS Open Bio. 2019, DOI: 10.1002/2211-5463.12617
Gast K, Schüler A, Wolff M, Thalhammer A, Berchtold H, Nagel N, Lenherr G, Hauck G, Seckler R. Rapid-acting and human insulins: Hexamer dissociation kinetics upon dilution of the pharmaceutical formulation. Pharm Res. 2017, DOI: 10.1007/s11095-017-2233-0
Wolff M, Zhang-Haagen B, Decker C, Barz B, Schneider M, Biehl R, et al. Abeta42 pentamers/hexamers are the smallest detectable oligomers in solution. Sci Rep. 2017, DOI: 10.1038/s41598-017-02370-3
Bremer A, Wolff M, Thalhammer A, Hincha DK. Folding of intrinsically disordered plant LEA proteins is driven by glycerol-induced crowding and the presence of membranes. FEBS J. 2017, DOI: 10.1111/febs.14023
Wolff M, Unuchek D, Zhang B, Gordeliy V, Willbold D, Nagel-Steger L. Amyloid beta Oligomeric Species Present in the Lag Phase of Amyloid Formation. PLoS One. 2015, DOI: 10.1371/journal.pone.0127865
Grüning CS, Klinker S, Wolff M, Schneider M, Toksoz K, Klein A.N., Nagel-Steger, L., Willbold, D., Hoyer, W. The off-rate of monomers dissociating from amyloid-beta protofibrils. J Biol Chem. 2013, DOI: 10.1074/jbc.M113.513432
Luers L, Bannach O, Stohr J, Wördehoff M.M., Wolff M, Nagel-Steger L, Riesner, D., Willbold, D., Birkmann, E. Seeded fibrillation as molecular basis of the species barrier in human prion diseases. PLoS One. 2013, DOI:10.1371/journal.pone.0072623