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."
- Nanoislands on silicon with switchable topological texturesNanostructures with specific electromagnetic patterns promise applications in nanoelectronics and future information technologies. However, it is very challenging to control those patterns. Now, a team at HZB examined a specific class of nanoislands on silicon with interesting chiral, swirling polar textures, which can be stabilised and even reversibly switched by an external electric field.
- Lithium-sulphur pouch cells investigated at BESSY IIA team from HZB and the Fraunhofer Institute for Material and Beam Technology (IWS) in Dresden has gained new insights into lithium-sulphur pouch cells at the BAMline of BESSY II. Supplemented by analyses in the HZB imaging laboratory and further measurements, a new picture emerges of processes that limit the performance and lifespan of this industrially relevant battery type. The study has been published in the prestigious journal Advanced Energy Materials.
- Largest magnetic anisotropy of a molecule measured at BESSY IIAt the Berlin synchrotron radiation source BESSY II, the largest magnetic anisotropy of a single molecule ever measured experimentally has been determined. The larger this anisotropy is, the better a molecule is suited as a molecular nanomagnet. Such nanomagnets have a wide range of potential applications, for example, in energy-efficient data storage. Researchers from the Max Planck Institute for Kohlenforschung (MPI KOFO), the Joint Lab EPR4Energy of the Max Planck Institute for Chemical Energy Conversion (MPI CEC) and the Helmholtz-Zentrum Berlin were involved in the study.