A pioneering basic research approach to harness the potential in highly complex pharmacologically interesting diterpenoid compounds
By humanity, diterpenoids have been widely used to remedy maladies as components of complex herbal extracts. However, individual diterpenoids are difficult to isolate in significant amounts and their complex structures render chemical synthesis almost impossible.
The focus will be on selected target compounds with strong structural homology with documented effect as antagonists on the k-opioid receptor. Using a unique combination of state-of-the-art technologies we can now separate and structurally characterize the individual diterpenoids present in complex herbal extracts, carry out screens defining their individual bio-activity and elucidate the biosynthesis of the best-performing candidates.
Subsequent heterologous expression in yeast offers an environmentally benign route to produce the compounds for more detailed characterization of in vitro bio-activity in the absence of stereochemical ‘pollutants’ and reduction of undesired effects. The results will guide combinatorial studies in which the biosynthetic enzymes from different plant species will be combined to obtain new-to-nature diterpenoids.
An interdisciplinary research approach is essential to achive these goals
Professor Birger Lindberg Møller (chair), Professor Dan Stærk, Professor Ulrik Gether
Birger Lindberg Møller (chair), Dan Stærk, Ulrik Gether, Irini Pateraki, Allison Maree Heskes, Sotirios Kampranis, Kenneth Kongstad, Kenneth Lindegaard Madsen, Claus Juul Løland, Søren G.F. Rasmussen.