Lipids (amphiphilic molecules) comprise an important group of bio-molecules. As part of the cell membrane they form a barrier which protects the inner part of the cell from the outer part, and provide a surface where many biological reactions occur. In addition, some of these lipids are involved in various signaling pathways. For example the lipid constituents of glycosphingolipid, ceramide and sphingosine are involved in apoptosis and proliferation, respectively. Other lipid likes have such interesting biological properties that knowledge about their mode of action is crucial. For instance novel biological tools can be development from broussonetines and analogs thereof, since they possess potent glycosidase inhibitory properties and jaspines which are cytotoxic. The diverse and challenging structures in combination with their activities make them very worthwhile research subjects for the (synthetic) bio-organic chemist. The BIOSYN group is active in all 4 research topics.
Current research in the BIOSYN group is directed to a broad range of synthetic chemistry of amphiphilic molecules. Within the synthetic methodology framework we develop a new multi-component reaction sequence the SAWU. This Ugi three component reaction sequence is facilitated for the construction of libraries containing polyhydroxylated pyrrolidines and piperidines. Adamantanemethanol proved to be a powerful substitute for the hydrophobic part of the amphiphilic molecules, extension towards functionalized diadamantane and triadamantane is currently ongoing.
In the drug discovery projects hydrophobic iminosugars are made, they can target crucial metabolic pathways which are involved in Gaucher disease, Type-II diabetes and certain cancers.
In the functional proteomics field we recently reported on the development of a set of amphiphilic molecules which act like chaperones to enhance misfolded proteins.
Gramicidin S, an amphiplic molecule with antimicrobial properties proved to be a fruitful study objective. Currently, the synthesis of new hydrophobic amino acids based on adamantane is in development. This novel hydrophibic peptidomimetics will be used to vary the amphiphilic character of Gramicidin S.