Metal atom dictates the structure: new concept for the construction of enzyme inhibitors
Complex natural products usually adopt precisely defined spatial structures that are of critical importance to their biological function. A substrate must fit precisely into the “pocket” of an enzyme in order to be converted. The same is true of drugs meant to influence the function of enzymes. The biggest challenge in this is to develop effective methods for the synthesis of agents with tailored three-dimensional structures. A team of British and American researchers headed by Eric Meggers is using metal atoms to give their agents the right shape. They have now successfully used this concept to develop a specific inhibitor for protein kinase Pim-1 based on a ruthenium complex.
Protein kinases play an important role in a large number of cellular regulatory mechanisms. The natural compound staurosporine is an effective inhibitor for the adenosine triphosphate (ATP) dependent protein kinases because it fits precisely into the ATP-binding cavity of these enzymes. Meggers and his team at the University of Pennsylvania (USA) and Oxford University (UK) used the structure of staurosporine as the starting point for the development of a more simply constructed metal-containing inhibitor. Staurosporine consists of a flat aromatic ring system and a sugar component. The scientists replaced the sugar with a ruthenium atom bound to two ligands. The ring system, which was slightly altered, also binds to the ruthenium as a ligand. Like a clamp, it surrounds the metal from two sides. Careful selection of the two other ligands—carbon monoxide and an five-membered aromatic ring—allowed the researchers to give their ruthenium complex a form that mimics the spatial structure of staurosporine and also fits into the ATP-binding cavity.
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Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
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Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
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