Our research mainly focusses on the following topics:
G protein signaling cascades: With new molecular probes and modulators towards novel pharmacological concepts
Towards understanding structural and dynamical determinants of G protein inhibition – rational design of novel subtype specific G-protein inhibitors
This project is part of a research unit initiative and has the goal to develop and investigate selective and cell permeable G protein inhibitors as novel pharmacological tools to specifically modulate/silence G protein signaling.
1. Schmitz, A. L. et al. “A new mechanism to interdict heterotrimeric Gαq protein function with small molecules: “trapping” Gαq in the empty pocket conformation”, 2014, Chem. Biol., 21, 890-902
2. Schrage, R. et al. “The analytical value of FR900359 to study Gq-regulated biological processes”, 2015, Nat. Commun., 6, 10156
3. Reher, R. et al. “Deciphering specificity determinants for FR900359-derived Gq alpha based on computational and structure-activity studies“, 2018, ChemMedChem, 13, 1634
The long-term objective of this research is to understand how ion channel function can be modified through specific interaction with natural peptidic toxins. In order to achieve this goal it is necessary to understand channel-toxin interaction on an atomistic level. Especially voltage gated potassium and sodium channels are in the scope of our investigations.
1. P. Heimer et al. “Conformational peptide isomers revisited: The impact of disulfide connectivity on structure and bioactivity”, 2018, Anal. Chem., 90 (5), 3321-3327
2. D. Tietze et al. “Molecular interaction of δ-conopeptide EVIA with voltage-gated Na+ channels”, 2016, Biochim. Biophys. Acta, 1860 (9), 2053-2063
Our long-term objective is to solve the mechanism of superoxide degradation through the enzyme Nickel superoxide dismutase (NiSOD).
1. D. Tietze et al. “Revealing the position of the substrate in NiSOD: a model study”, 2011, Angew. Chem. Int. Edit., 50(13), 2946-2950
2. D. Tietze* et al. “New insights into the mechanism of nickel superoxide degradation from studies of model peptides”, 2017, Sci. Rep., 7 (1), 17194
3. D. Tietze* et al. “Ni(II)-complex formation and protonation states at the active-site of a nickel superoxide dismutase-derived metallopeptide: implications for the mechanism of superoxide degradation”, 2018, Chem. Eur. J., doi:10.1002/chem.201803042
Aside from our strong focus on NMR spectroscopy, we employ a wide range of different techniques (e.g. UV-Vis, Stopped-Flow-Kinetics). Typically, NMR spectroscopy is used to investigate structural and dynamical aspects of our systems of interest. These data are then used for modeling purposes (MD Simulations, DFT) to generate an atomistic understanding of the catalytic mechanism of superoxide degradation or drug binding to Gproteins or ion channels.