Natural Products Research Group
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)
DMPB is an open access biobank of all Danish medicinal plant species – with the aim to facilitate interdisciplinary and inter-organisational investigations of known and unknown bioactive compounds with drug development potential. DMPB is set to open ultimo 2020.
Pharmacopoeias reveal 330+ species of Danish plants offered as herbal drugs in pharmacies through the last 400 years – hinting the presence of bioactive compounds. We propose that modern approaches to identifying and evaluating compounds in historical herbal drugs may lead to valuable discoveries and stepping-stones to address e.g. metabolic and inflammatory disorders, cancer, and infectious diseases. Danish Medicinal Plant Biobank facilitates state-of-the-art natural products research via plant collection, chemical and pharmacological screening, documentation, storage, and preparation – and welcome inter-organisational research collaborations.
Funding sources: Alfred Benzon Foundation
Contact: Postdoc Jens Soelberg, jso@sund.ku.dk
Group members
| Name | Title | Phone | |
|---|---|---|---|
| Dohn, Sussi Rosenørn | Laboratory Technician. | +4535332460 | |
| Kjærulff, Louise | Academic Research Staff | +4535326544 | |
| Kongstad, Kenneth Thermann | Associate Professor | +4535336411 | |
| Liang, Chao | Postdoc | ||
| Mc Nair, Laura Mikél | Postdoc | +4535326132 | |
| Petersen, Malene Johanne | PhD Fellow | +4535330251 | |
| Stærk, Dan | Professor | +4535336177 | |
| Önder, Arife | Laboratory Technician | +4535336518 |