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Scientists at the University of Magdeburg succeed in fully synthesizing one of the strongest natural cytotoxic substances
Chemists at Otto von Guericke University Magdeburg have succeeded for the first time in synthetically recreating the naturally occurring substance, Disorazol Z1, by using a highly efficient process. With the world's first total synthesis of this highly active natural compound, the team led by Senior Professor Dr. rer. nat. habil. Dieter Schinzer from the Institute of Chemistry has, by its own account, achieved a scientific breakthrough.
Disorazol Z1 is among the planet's most active cytotoxic compounds, in other words it is able to prevent the division of human and animal cells to a high level of effectiveness as well as to destroy cells. The natural substance is produced by myxobacteria, which are prevalent worldwide and frequently occur in organic wastes such as goat manure. Scientists discovered the bacterial strain some years ago, isolated the active ingredient and since then have been conducting scientific studies on it with a view to developing possible cancer treatments.
“The substance is extremely active,” explains Professor Schinzer. “We are talking about picomolar concentrations, that is, twelve zeros after the decimal point. That is why, for safety reasons, we initially only manufactured two milligrams and took strict safety precautions - using gloves, face masks and closed fume cupboards. Had we produced larger quantities, this may have had health consequences.
The chemist goes on to say that since Disorazol Z1 could previously only be produced naturally by bacteria, its chemical synthesis is a great step forward for cancer research. A crucial advantage of synthetic production is the possibility of modifying the compound in a targeted way and thus optimizing its biological properties for medical applications.
“We have imitated nature, but with one crucial advantage. Bacteria only produce Disorazol Z1 in a certain form, but we can systematically adapt it and optimize it for medical uses.”
The major medical optimization task is to change the molecule so that it first attaches itself to a certain protein, an antibody, and thus can be guided specifically to the tumor. Then the active substance is released and selectively impedes the division of the tumor cells. The scientist explains that cell death, known as apoptosis, will only occur where it is desirable in future. “In collaboration with industrial partners, the substance will now be developed further so that it targets cancer cells, while healthy cells are largely spared.”
The scientist goes on to clarify that, moreover, the total synthesis of this substance was also a major challenge, because it was a first synthesis. “We developed innovative strategies in order to construct the molecule in several stages. State-of-the-art chemical techniques and analytical methods were used to confirm the precise structure of the synthesized compound.”
The next steps after this research success are to rapidly patent and publicize the discovery. Furthermore, the team of researchers plans further investigations into the medical applicability of the substance and optimizing the synthesis for possible industrial applications.
The project was financed from state funds as well as by the European Fund for Regional Development (EFRD). Overall, funding amounted to around 1.7 million euros.
Prof. Dr. rer. nat. Dieter Schinzer, Institute of Chemistry, Faculty of Process and Systems Engineering, Tel.: +49 (0)391 675 8673, email: dieter.schinzer@ovgu.de
Prof. Dieter Schinzer with the model of the disorazole molecule.
Jana Dünnhaupt
Uni Magdeburg
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Prof. Dieter Schinzer with the model of the disorazole molecule.
Jana Dünnhaupt
Uni Magdeburg
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