In the development of new drugs, photoaffinity labels (PALs) are a versatile tool to investigate the interaction between a receptor and a drug or a ligand. Researchers working with Stephanie Grond at the University of Tübingen and Paultheo von Zezschwitz at the University of Marburg have now developed a new class of PALs that can be attached to the ligand in a single step, thus causing less modification of its structure, as they report in the European Journal of Organic Chemistry. The group has tested the new labels on an enzyme that is linked to osteoporosis and cancer.
When PALs are used to study a specific ligand, the ligand is firstly decorated with a chemical group that can be activated when exposed to ultraviolet light, whereupon it irreversibly binds to the receptor to form a stable complex. This complex can then be thoroughly studied, e.g., by fragmentation of the receptor. Typically, formation and fragmentation of the ligand–receptor complex is traced by monitoring special tags that are incorporated into the complex. However, these tags are problematic due to high costs and size restrictions, and frequently, the tagged fragments cannot be detected among the vast excess of untagged fragments. Therefore, any potential to study the complexes is lost. Finding new ways to separate the tagged fragments from the untagged ones is one of the major challenges facing scientists today.
Grond and von Zezschwitz, together with the help of their biology colleagues Markus Huss and Helmut Wieczorek at the University of Osnabrück, have been studying V-ATPase, which is an enzyme that has been linked to osteoporosis and some cancers, to determine its mode of inhibition. To do so, they have developed a new fluorous photoaffinity label (F-PAL) that can be attached to the ligand in one step, as both the activator and the tag are contained within the same compound. The F-PAL contains a long carbon chain that is fully substituted with fluorine atoms instead of the usual hydrogen atoms. By using a special separation technique that is specific to fluorine-containing compounds, compounds with a high fluorine content can be easily “fished out” from untagged compounds. Once the tagged fragments of the ligand–receptor complexes are isolated, they can be analyzed to unravel the exact function of the drug, which could give scientists some valuable insight into how diseases such as osteoporosis and cancer can be fought.
Author: Stephanie Grond, Eberhard-Karls-Universität Tübingen (Germany), http://www.grond.chemie.uni-goettingen.de/
Title: New Fluorous Photoaffinity Labels (F-PAL) and Their Application in V-ATPase Inhibition Studies
European Journal of Organic Chemistry, Permalink: http://dx.doi.org/10.1002/ejoc.200901463
Make way for the mini flying machines
21.03.2018 | American Chemical Society
New 4-D printer could reshape the world we live in
21.03.2018 | American Chemical Society
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.
In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...
Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...
19.03.2018 | Event News
16.03.2018 | Event News
13.03.2018 | Event News
21.03.2018 | Physics and Astronomy
21.03.2018 | Materials Sciences
21.03.2018 | Life Sciences