Subproject 6

Active ingredients and bioavailability

 

The goal of this subproject is divided into two different research fields, which have the aim to identify novel and known natural substances for the modulation of Endoplasmic-Reticulum-Associated-Degradation (ERAD). Within the topic of "active ingredients" the research group will produce different plant extracts from marine sources or native plants such as sea buckthorn, elder and hops. Together with our medicinal project partners these plant extracts will be investigated to understand their mode of operation against ER-stress. The extraction of the plant material is carried out with the help of microwaves, which is a common, gentle and fast extraction method. The containing plant extracts are going to be tested for efficiency in cell culture assays and, where available, also compared with the mode of action of pure substances. The active extracts will then get fractionated by means of preparative high-performance liquid chromatography and analyzed for their ingredients using gas chromatography-mass spectrometry (GC/MS) and liquid chromatography-mass spectrometry (LC/MS). Thereafter, the active substances can be identified and isolated. Starting from known targets (biomolecules to which other molecule can bind, resulting in a change in their behavior or function) the research group will investigate secondary plant compounds like flavonoids, for example apigenin or quercetin, which are found in a number of native plants. Furthermore, in a next step the isolated active substances will be modified by the treatment with glycosidases as well as with chemical methods. So, the sugar residues can be split off to newly determine changes of the effectiveness in the assay.

The second research field is dedicated to "bioavailability". Here, the research group will carry out the specific derivatization of individual functional groups of flavonoids and lignans as well as the isolated and the newly synthesized drug candidates from LIKAT institute (subproject 7). This gives the opportunity to significantly improve the drug availability for the cells and to influence the potency of the potential drug candidates. A crucial role will play the glycosylation with different sugars. In addition to glycosyltransferases, a number of transglycosidases are described and commercially available in the literature, which are used for these purposes. The majority of the so far known targets are poorly water-soluble despite the numerous hydroxy groups, so that bioavailability is also restricted. In nature, this issue is solved by the binding with carbohydrates, partly with charges, so that the plant constituents can be stored in the vacuoles of the cells. This subproject is going to adapt this approach by regioselective glycosylation. In addition, a number of further methods are already used for the improvement of the bioavailability of drugs. These are inclusion in micelles, storage in cyclodextrins or crown ethers or adsorption on hydrophilized nanoparticles. As a new approach, the research group will investigate mixtures with ionic liquids as they are able to dissolve hydrophobic substances despite their ionic structure. By using biocompatible ionic liquids, for example on the basis of amino acids or carbohydrates, this also improves the availability in a physiological environment.

 


Supervisors

Prof. Dr. rer. nat. Udo Kragl

Dr. rer. nat. Christina Oppermann

 

Team

Manuel Gronbach

 

Former employees

Ole Celmer

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