In 1957, shepherds in Idaho (USA) discovered that when pregnant sheep ate lilies of the species Veratrum californicum (corn lily, California false hellebore), their lambs were born with only one eye in the center of their foreheads, like a cyclops.
The trigger for this was found to be the alkaloid cyclopamine. Cyclopamine has proven to be an effective candidate for cancer therapy in adult humans and is now undergoing clinical trials. A research team at the Universities of Leipzig (Germany) and Thessaloniki (Greece) has now developed a new synthetic pathway for the production of cyclopamine.
As they report in the journal Angewandte Chemie, the scientists, led by Athanassios Giannis, are confident that their research results will help to broaden our understanding of the structure–activity relationships of cyclopamine and to develop cyclopamine analogues with tuned bioactivities.
Cyclopamine is the first inhibitor of the hedgehog signal-transduction pathway, which is used by cells to react to external signals. The signaling pathway is named for its ligand “hedgehog”, a signal protein that carries out an important function in embryonic development. Malfunction of this signaling pathway leads to massive deformations in the course of embryonic development, such as cyclopia, and can cause cancer in adults. Inhibition of this pathway is a new possible cancer treatment.
Until now, there has been no efficient synthesis for cyclopamine. The structure of this unusual steroidal alkaloid contains many peculiarities that make synthesis difficult. The German and Greek team has now overcome these difficulties to develop an efficient twenty-step synthetic strategy starting from commercially available dehydroepiandrosterone, a natural steroid hormone. The strategy is based on biomimetic and diastereoselective transformations. The researchers achieved an overall yield of 1 %, which is a good result for such a tricky synthesis. In addition, small modifications in the reagents used allow this strategy to be used to produce cyclopamine analogues that do not occur in nature. The scientists aim to use these analogues to further examine the biological activity of this interesting natural product and then to adjust the activity to develop a new anti-tumor agent.Author: Athanassios Giannis, Universität Leipzig (Germany),
Angewandte Chemie International Edition, doi: 10.1002/anie.200902520
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy