Petra Kovaříček Research Group
The Start-up grant of the Experientia Foundation for 2020 went to the University of Chemistry and Technology in Prague. It was awarded to Dr. Petr Kovaříček, who established his research group focused on dynamic surface chemistry in January 2021.
Petr Kovaříček studied organic chemistry at the University of Chemistry and Technology, and received his doctorate from the Nobel Prize winner J.M. Lehn at the University of Strasbourg in France. He worked at Humboldt University in Berlin and at the J. Heyrovsky Institute of Physical Chemistry, Academy of Sciences of the Czech Republic. Now, thanks to the start-up grant of the Experientia Foundation he is coming back to its alma mater – the University of Chemistry and Technology in Prague.
“We are developing modern organic materials for innovative catalysts and adaptive electronics at the University of Chemistry and Technology in Prague,” Petr Kovaříček explains.
Most of the current electronic components, diodes, LEDs, chips and photovoltaic cells, consist of thin layers of various materials. The fact, that a given component then delivers a function, is determined by the flow of energy and charge in between the layers.
Each material the device is composed of must fulfil a number of very limiting criteria and have very precisely optimized properties, in order for a charge to flow between the layers in a controlled manner. Therefore, development of these materials is very demanding and we know relatively few of them.
“Our research group is approaching this process upside down. Instead of looking for a material that meets the criteria, we set the criteria and let the chemical system create the material for us,” Petr Kovaříček says.
How does it work? Imagine the surface of a material, such as silicon. Its inherent properties are given by what atoms and in what arrangement it is composed of.
“By agents that react with the surface, we can influence how the surface interacts with other molecules and thereby instruct the reaction network to preferentially form molecules that provide some desired function of the material,” Petr Kovaříček explains.
“We apply a solution of a large number of species to the surface, a whole chemical library, that interacts with the surface. When we use a stimulus, such as light of a certain wavelength, we affect only those substances from the whole library that absorb this wavelength. Absorbing a photon also alters the properties of this species and its ability to interact with the surface changes. In this way we can control how the layers assemble and the same principle can be used to make them work — shine like an LED, or generate a charge that will catalyze reactions,” Petr Kovaříček says.
“Our approach to organic material chemistry doesn´t focus on specific chemical bonds, structures, non-bonding interactions or even individual reactions. We see the world as an interconnected system, a dynamic system of molecules. These molecules share an environment, they affect each other and, for example, react with each other. We study the whole reaction network! This is an incredibly fascinating and almost unexplored direction of research, and thanks to a start-up grant from the Experientia Foundation, we can push this area forward,” Petr Kovaříček adds.
The Experientia Foundation supported Petr Kovaříček’s research group for 3 years with a start-up grant in the total amount of 6 million CZK.
Project: Dynamic Systems Chemistry
Location: University of Chemistry and Technology in Prague
Ondřej Baszczyňski Research Group
The first historic recipient of an Experientia Foundation start-up grant is the young scientist Dr Ondřej Baszczyňski. Previously, this organic chemist worked in the research groups led by Professor Antonín Holý and Dr Zlatko Janeba at the Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic. He established his own research group at the Science Faculty of the Charles University in Prague on 1 January 2019 and receives annual funding of CZK 2 million from Experientia Foundation and another CZK 0.7 million from the host institution for a period of three years. Baszczyňski won the internationally acclaimed competition organised by the Experientia Foundation with his project for ProTide based drug delivery vehicles.
The Search for a Smart Drug
The chemist Ondřej Baszczyňski wants to “teach” drugs how to take effect in the human body only where, and primarily when, they have to. These “smarter” drugs might lead to a breakthrough in the treatment of certain illnesses such as non-systemic infections or cancer.
Baszczyňski’s plan is truly quite ambitious and it is not lacking in associated risks either – his aim is to focus on the targeted delivery of biologically active compounds to their place of action with the use of phosphate-based prodrugs. The above is a more complicated explanation of the solution he is looking for in his laboratory.
The simpler explanation is as follows: Medicine today has many effective drugs at its disposal; however, they have many side effects such as toxicity, and/or are either eliminated from the body too quickly or poorly absorbed by human cells. These are some of the reasons why attention is being focused on “prodrug strategy”: specific modifications of known drugs which lead to the delivery of an effective substance to the required site in the human body while diminishing the drug’s adverse effects.
According to Baszczyňski: “Their greatest potential is in the field of cancerostatics , i.e. drugs used to treat cancer. Although cancer treatment has greatly advanced, there are still several types of cancer for which the drugs have many side effects. If we are able to successfully modify them in such a way that they do not affect all of the cells in the human body, but act only in those places where they should and at exactly the right moment, cancer treatment could move forward quite a bit.”
Three words in the explanation are of key importance: “the right moment”. There are a great number of scientists focusing on how to deliver a substance to the point in the body where there is an inflammation, infection, or tumour, and, thanks to them, research in this area continues to advance. However, Baszczyňski and his team want to chiefly look at how to ensure that the active substance is released at the best time in addition to it taking effect only at the afflicted site.
“This is why we want to investigate primarily the so-called ‘self-cleaving spacers’, which connect the effective therapeutic agent with the recognition group – the so-called ‘ligand’ – which is that part which recognises the target site where the drug should be delivered. Our spacer must be capable of chopping off the drug at just the right time so that it is released when it should be,” says Baszczyňski. A simpler solution would be to produce these spacers from, for example, artificial polymers, which could, however, be toxic for the human body an represent a needless burden. This is why Baszczyňski is working on developing spacers composed only from amino acids and phosphates, that is to say on a purely natural basis, so they are biologically completely harmless.
A similar solution already exists in clinical practice in the case of, for instance, nucleotide prodrugs with antiviral effects or for the antibody-drug conjugates used in cancer treatment. However, for many other drugs, which are the ones that Baszczyňski intends to focus on, the concept is still only at a purely theoretical level. This is one of the reasons why this particular research might one day lead to a breakthrough in medicinal chemistry. “We are still at the absolute beginning. Now, we first have to optimise a series of spacers and find the one that will be stable enough under physiological conditions and yet also able to self-cleave and be absorbed when it is needed. Only after we have identified it will we be able to apply it to known drugs, and it will be only then that we will see if it is worth patenting,” explains the researcher.
Excerpt from the text of the editor, Pavel Kalous, published in the Marwick magazine (March 2019). Published with courtesy of the editors.