Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Starving Out Malaria Parasites

17.03.2006


New class of selective inhibitors paralyze essential plasmodium enzymes



The most dangerous variant of the malaria parasite, Plasmodium falciparum, infects up to 600 million people every year. The search for new effective therapies is thus an urgent area of research. An international team headed by François Diederich has now found a new point of attack: using a novel class of inhibitors, the researchers aim to block certain plasmodium enzymes known as plasmepsins, “starving out” the malaria parasite.

Plasmepsins belong to the family of aspartic protease enzymes. They dismantle human hemoglobin to deliver the amino acids that plasmodia need in order to grow. In developing a new inhibitor, it is important to ensure that it blocks all of the plasmodium plasmepsins while remaining inactive toward human aspartic proteases.


The team of researchers from the Swiss Federal Institute of Technology (ETH) in Zurich, the University of Victoria (Canada), Washington University, St. Louis (USA), and Actelion Pharmaceuticals in Allschwil (Switzerland) started with the previously determined spatial structure of one of the plasmepsins, plasmepsin II. This enzyme has a sort of pocket, formed by the opening of a peptide loop, which seemed to be a suitable point of attack for an inhibitor. On the basis of computer simulations, the researchers successfully developed a family of molecules that fit well into this cavity. The central structural element of these molecules is a bicyclic diamine framework: a six-membered ring of carbon atoms in which two opposite carbon atoms are additionally bridged by the nitrogen of the amino group. A second amino group is bound to a neighboring carbon atom. Like a pincer, the diamine framework clamps onto the catalytic dyad (the two catalytically active aspartate groups) of the plasmepsin. An additional side group fits into a second, adjacent pocket (S1/S3-cavity) of the enzyme.

Enzymatic assays pointed the way to the most effective molecules. It was demonstrated that these did not only block plasmepsin II, for which they were specifically tailored: plasmodium plasmepsins I and IV were both even more strongly inhibited. These enzymes clearly have a very similar structure. In contrast, human aspartyl proteases seem to have a completely different spatial structure because they are not affected at all. In cell cultures of plasmodium-infected red blood cells, the new inhibitors were able to inhibit the growth of the parasites. “We are now trying to further improve the activity of the inhibitors,” says Diederich, “with the goal of developing a new class of antimalaria agents.”

François Diederich | Angewandte Chemie
Further information:
http://www.diederich.chem.ethz.ch/
http://pressroom.angewandte.org

More articles from Life Sciences:

nachricht Study shines light on brain cells that coordinate movement
26.06.2017 | University of Washington Health Sciences/UW Medicine

nachricht New insight into a central biological dogma on ion transport
26.06.2017 | Aarhus University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Study shines light on brain cells that coordinate movement

26.06.2017 | Life Sciences

Smooth propagation of spin waves using gold

26.06.2017 | Physics and Astronomy

Switchable DNA mini-machines store information

26.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>