Department of Chemistry of Natural Compounds

Granting Departments:	Department of Chemistry of Natural Compounds
Study Programme/Specialization:	Biochemistry and Bioorganic Chemistry ( in Czech language )
Supervisor:	Ing. Michal Jurášek, Ph.D.

Annotation

The natural products Taxol and vinblastine are established drugs in the treatment of various malignant pathologies. Colchicine is an alkaloid used in the treatment of severe inflammation. Although colchicine has potent antitumor properties, no derivative has yet reached the market. The potential of colchicine for targeting γ-tubulin is also significant. The group has original and unpublished knowledge on this effect. The main problem with Taxol is the increasing resistance of tumors to this treatment. The aim of the work will be (1) to synthesize new colchicine derivatives designed as γ-tubulin inhibitors, (2) to design and synthesize new potent Taxol derivatives with reduced P-gp induction, and (3) to design and synthesize new precursors of Taxol and vinblastine designed for binding to a polymer targeting tumor tissue.

Institute of Microbiology of the CAS

Granting Departments:	Department of Chemistry of Natural Compounds Institute of Microbiology of the CAS
Study Programme/Specialization:	Biochemistry and Bioorganic Chemistry ( in English language )
Supervisor:	doc. Ing. Kateřina Valentová, Ph.D.

Annotation

Flavonoids are plant food components that are known to be intensively metabolized in the gut and to interact with and influence the composition of the gut microbiome. Flavonoids are also subject to rapid biotransformation in the II phase, whereby mainly corresponding sulfates and glucuronides are formed. The biotransformation of polyphenols by the gut microbiota also leads to cleavage of the C-ring and the formation of simple phenolic substances. The aim of this PhD project is the optimization of chemoenzymatic methods for the synthesis of a library of natural flavonoids (myricetin, luteolin, kaempferol, naringenin, hydroxyphenylacetic acid and hydroxyphenylpropionic acid) and their metabolites (sulfates, glucuronides and depsides). Natural and mutant enzymes from bacterial and fungal sources (arylsulfotransferases, glucuronidases, quercetinase) are used for this purpose. These enzymes are expressed in microbial expression systems (E. coli, P. pastoris), characterized and optimized for the synthesis of the desired metabolites. The compounds are then used as standards for metabolic studies carried out in collaboration with our partner laboratories.

Institute of Organic Chemistry and Biochemistry of the CAS

Granting Departments:	Department of Chemistry of Natural Compounds Institute of Organic Chemistry and Biochemistry of the CAS
Study Programme/Specialization:	Biochemistry and Bioorganic Chemistry ( in English language )
Supervisor:	Dr. habil. Ullrich Jahn

Annotation

The axinellamines belong to the most complex alkaloids with interesting biological properties. With this project biomimetic approaches will be explored to enable short total syntheses of the natural products themselves and of analogs. Their biological profile will be investigated in collaboration.

Granting Departments:	Department of Chemistry of Natural Compounds Institute of Organic Chemistry and Biochemistry of the CAS
Study Programme/Specialization:	Biochemistry and Bioorganic Chemistry ( in English language )
Supervisor:	Mgr. Radim Nencka, Ph.D.

Annotation

The Ph.D. student will design and synthesise novel methyltransferase (MTase) inhibitors targeting viral, fungal or human MTases. The student will use in silico approach to speed up the development of potential drugs, but the main part of the assignment will be the organic synthesis. Preparation of suitable ligands bearing a fluorescent tag will enable the efficient development of a screening assay.

Granting Departments:	Department of Chemistry of Natural Compounds Institute of Organic Chemistry and Biochemistry of the CAS
Study Programme/Specialization:	Biochemistry and Bioorganic Chemistry ( in English language )
Supervisor:	Mgr. Tomáš Pluskal, Ph.D.

Annotation

Our lab combines cutting-edge experimental (e.g., LC-MS, metabolomics, RNA-seq) and computational (e.g., bioinformatics, molecular networking, machine learning) approaches to develop new workflows for the discovery and utilization of bioactive molecules derived from plants. This project will focus on screening many plant species using liquid chromatography mass spectrometry to discover and isolate unique chemicals (metabolites), including basic characterization of their bioactive potential.

Granting Departments:	Department of Chemistry of Natural Compounds Institute of Organic Chemistry and Biochemistry of the CAS
Study Programme/Specialization:	Biochemistry and Bioorganic Chemistry ( in English language )
Supervisor:	Dr. habil. Ullrich Jahn

Annotation

We just accomplished approaches to glycine alkoxyamines, which hold large promise in bioconjugation. With this project the potential of these non-natural amino acid derivatives for approaching new peptide architectures will be explored.

Granting Departments:	Department of Chemistry of Natural Compounds Institute of Organic Chemistry and Biochemistry of the CAS
Study Programme/Specialization:	Biochemistry and Bioorganic Chemistry ( in English language )
Supervisor:	Mgr. Radim Nencka, Ph.D.

Annotation

The PhD student will focus on the design and organic synthesis of new methyltransferase inhibitors, whether derived from viral, fungal, or human sources. In the course of developing these compounds, the candidate will employ in silico molecular modeling to streamline and accelerate the search and optimization of inhibitors. Nonetheless, the main emphasis of the project will remain on the organic synthesis of potential therapeutic agents. Additionally, the project will include the preparation of ligand analogs equipped with suitable tags, whether fluorescent or functional (e.g., biotin for pull-down assays, thalidomide for PROTAC technology).

Granting Departments:	Department of Chemistry of Natural Compounds Institute of Organic Chemistry and Biochemistry of the CAS
Study Programme/Specialization:	Biochemistry and Bioorganic Chemistry ( in English language )
Supervisor:	Mgr. Tomáš Pluskal, Ph.D.

Annotation

Our lab combines cutting-edge experimental (e.g., LC-MS, metabolomics, RNA-seq) and computational (e.g., bioinformatics, molecular networking, machine learning) approaches to develop new workflows for the discovery and utilization of bioactive molecules derived from plants. The aim of this project will be to engineer new microbial platforms for the bioproduction of terpenoid precursors and terpenoids derived from them.

Granting Departments:	Department of Chemistry of Natural Compounds Institute of Organic Chemistry and Biochemistry of the CAS
Study Programme/Specialization:	Biochemistry and Bioorganic Chemistry ( in English language )
Supervisor:	Dr. habil. Ullrich Jahn

Annotation

With the project, synthetic approaches to complex indoloterpene and their analogs displaying wide-ranging biological activity will be developed.