Stærk lab
We develop analytical techniques for discovery of bioactive peptides and small molecules as drug leads for treatment of type 2 diabetes, infectious diseases and cancer - and we investigate natural sources like plants, marine organisms, food by-products, endophytic fungi, and extremophilic microorganisms
We develop analytical techniques for discovery of bioactive peptides and small molecules as drug leads for treatment of type 2 diabetes, infectious diseases and cancer - and we investigate natural sources like plants, marine organisms, food by-products, endophytic fungi, and extremophilic microorganisms
A key focus area in the Natural Products Research group is development and application of new technologies. The below represents some recent developments and use of state-of-the-art technologies for natural products research.
- NMR-based metabolomics
- Hyphenated HPLC-SPE-NMR/high-resolution bioassay
- Fungal Fight
- Combining Ligand Fishing Technologies with HPLC-SPE-NMR for Facilitated Discovery of Bioactive Principles from Marine Macroalgae:
Project summary: The marine flora, including macroalgae, is an invaluable source of unique bioactive molecular scaffolds such as brominated phenols and various oxygen-, nitrogen-, and sulphur containing heterocycles. It is furthermore a potential sustainable source of bioactive constituents. However, the biochemical complexity of the marine ecosystem and inhabiting algal species poses a significant challenge in drug discovery.
This project aims at developing a ligand-fishing technology, in which target enzymes are immobilized on a solid support, and combine it with HPLC-HRMS-SPE-NMR analysis. The resulting ligand-fishing/HPLC-HRMS-SPE-NMR technology will be used to screen marine macroalgae for potential bioactive principles for type-2 diabetes. Affiliation with Copenhagen Small-Molecule NMR Centre ensures access to state-of-the-art instrumentation, and a stay in the laboratories of Prof. Irving W. Wainer, National Institute of Health, ensures internationalization.
High-resolution biochromatography, where microfractionation into 96-well microplates and subsequent bioassaying provides a biochromatogram that can pinpoint HPLC peaks correlated with bioactivity:
Ligand fishing, where enzymes are immobilized (via covalent bond) on magnetic beads, whereafter the enzyme-bead complexes are used to fish out ligands of complex mixtures:
Bioactivity-correlated metabolomics, where chemical fingerprints (e.g., 1H NMR spectra or LC-HRMS chromatograms) are color-coded according to the IC50values of the crude extract. Subsequent analysis of the score and loading plots allows easy pinpointing of principle components and loadings correlated with bioactivity:
Bioaffinity NMR, where saturation of enzymes, receptors and/or transporters are transferred to ligands with intermediate on/off rates, whereby difference spectra from experiments with and without saturation provides spectra with signals for a ligand’s protons that are in close proximity with the enzyme during binding in the active site:
The Natural Product Research Group are also dedicated to educating the next generation of pharmacists, and we teach BSc students about ‘Drugs from Nature, and PhD students about ‘NMR Techniques in Drug Research’. Our dedication and prioritization of teaching was acknowledged by Professor Dan Stærk being awarded Teacher of the Year at PharmaSchool in 2018 and Assistant Professor Kenneth Kongstad awarded Teacher of the Year in 2019
Drug discovery from nature using advanced bioanalytical technology (link to webpage)
Danish Medicinal Plant Biobank facilitates data-driven sampling and high-throughput screening for drug lead compounds and biological/pharmacological activity in 300+ Danish medicinal plant species.
DMPB is open access and welcomes public and private research cooperation
Group members
Name | Title | Phone | |
---|---|---|---|
Khanam, Sofia | Visitor | ||
Kjærulff, Louise | Research Consultant | +4535326544 | |
Zhu, Jianzhong | PhD Student |