Chemical Biology

Head of Department of Chemical Biology and Genetics: Karel Doležal

 

This research program includes namely the development of new molecules that are able to interact with key proteins of regulatory and signalling pathways in cells. Research in this field has a long tradition in Olomouc, the research team of the Centre has already prepared a wide range of biologically active derivatives of naturally occurring compounds, including topolins, olomoucine, roscovitine, betulines, pyratine, chemopreventive compounds and others. Research will be focused on the identification and development of new compounds that are able to reach the targets in key cell processes, i.e. cell cycle regulation and apoptosis. The aim of the research will be the development of biomolecules targeting proteins/genes that play important roles in tumour cells during malignant transformation. The second part of the research will be dedicated to targeted plant growth regulators, mainly those that are able to modulate phytohormone pathways in plants. We will synthesize new chemical compounds using classical and combinatorial chemistry, isolate and identify natural substances with demonstrable enzyme-inhibitory, protein-deregulatory, chemopreventive, plant growth-regulating and general biological effects. We will introduce new modifications of very active chemical compounds in order to develop very potent inhibitors/activators and/or (ant)agonists effective in micro- and nanomolar concentrations.

A part of this subproject will be oriented on the development and implementation of suitable tests for routine, usually automated, screening of current chemical libraries, natural substances, extracts from plant, fungi and micro-organisms and also newly prepared chemical compounds. Biological activity of new derivatives, including their interactions with key enzymes of cytokinin phytohormone perception and metabolism, will be studied and tested in plant bioassays. Growth-regulatory properties of newly prepared compounds will be tested using high-throughput phenotyping system under normal and stress conditions and also in field experiments on economically important crops.