Cancer research at BESSY II: Binding Mechanisms of Therapeutic Substances Deciphered
The study is displayed on the cover of the journal Chemmedchem. © Chemmedchem/VCH Wiley
In tumor cells, the DNA is altered in comparison to normal body cells. How such changes can be prevented or inhibited is an exciting field of research with great relevance for the development of cancer treatments. An interdisciplinary team has now analysed the possible binding mechanisms in certain therapeutic substances from the tetrazole hydrazide group using protein crystallography at BESSY II.
Certain proteins such as human histone demethylases, including the KDM4 protein, play a role in the development of tumour cells. They bind to the DNA and modify it so that the cell can become cancerous. Therapeutic substances that are able to inhibit or even reverse such changes are of particular interest.
Biochemist Prof. Dr. Udo Heinemann from the Max Delbrück Centre in Berlin-Buch is investigating such processes. In cooperation with chemists led by Prof. Dr. Andreas Link from the University of Greifswald and the team led by Dr. Manfred Weiss at the HZB, he has now investigated how and where certain therapeutic substances from the tetrazole hydrazide group dock to these protein molecules and thus inhibit their harmful effect.
KDM4 protein crystals analysed
Link initially produced variations of tetrazole hydrazide substances. For structural analysis, crystals had to be grown from KDM4 proteins - a difficult task that Dr. Piotr Malecki and Manfred Weiss had taken on at the HZB. The KDM4 protein crystals were then soaked in a specific substance before being analyzed with strong X-rays on the MX beamlines of BESSY II. A refined analysis showed not only the three-dimensional architecture of the KDM4 protein, but also exactly where the active substances had docked to the KDM4 molecule.
"This class of substances has not yet been structurally investigated," explains Manfred Weiss. And Udo Heinemann from the MDC explains: "We will now evaluate where there are opportunities to dock even stronger within the 3D structure of the KDM4. Then we might also be able to develop drugs that inhibit the KDM4 even more and thus have the potential to become a therapeutic."
- Magnon momentum microscopy: A new window into nanoscale spin-wavesAn international team lead by the Max Born Institute has developed a new type of momentum microscopy to image magnons — the quanta of collectively excited spins — directly in two-dimensional reciprocal space using soft X-rays. Measurements have taken place at BESSY II and PETRA III, first author ist the HZB physicist Steffen Wittrock. Owing to its remarkable sensitivity, simplicity, and access to nanometer-scale wavelengths, this novel technique establishes a powerful and versatile platform for exploring nonlinear magnon interactions, which are promising for future computing schemes.
- X-ray analysis reveals overpainted fascist symbolsErich Mercker was a successful painter during the Nazi era and in the years that followed. After 1945, he covered up Nazi symbols in at least one of his paintings. With an interdisciplinary team, physicist Dr Ioanna Mantouvalou reports on this study in the Nature Journal Heritage Science.
- Magnetic field during catalyst synthesis triples ammonia yieldApplying an external magnetic field during the synthesis of CoFe₂O₄ electrocatalysts triples the ammonia yield during electrocatalytic conversion. The magnetic field alters the surface states of the spinel oxide thin films, making catalytically active sites more accessible. In the journal 'Advanced Functional Materials', a team led by Marcel Risch at HZB and Sanjay Mathur at University of Cologne demonstrates a scalable strategy for developing next-generation electrocatalysts for efficient and sustainable chemical production.