Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC
GLOBETECH MEDIA

New Generation of Malaria Drugs Block Myristoylation in the Parasite

By BiotechDaily International staff writers
Posted on 02 Jan 2014
Image: Blood smear from a P. falciparum culture. Several red blood cells show ring stages inside them, while close to the center there is a schizont and on the left a trophozoite (Photo courtesy of Wikimedia Commons).
Image: Blood smear from a P. falciparum culture. Several red blood cells show ring stages inside them, while close to the center there is a schizont and on the left a trophozoite (Photo courtesy of Wikimedia Commons).
Researchers have identified the enzyme N-myristoyltransferase (NMT) as a target for a new generation of drugs to be used for the treatment of malaria.

Investigators from several research institutions in the United Kingdom taking part in a five-year project funded by the British Councils for Medical Research, Engineering and Physical Sciences Research, and Biotechnology and Biological Sciences Research recently described an integrated chemical biology approach that they had used to explore protein myristoylation in the major human malaria parasite Plasmodium falciparum.

N-myristoylation is a cellular process in which a myristoyl group (derived from myristic acid) is covalently attached via an amide bond to the alpha-amino group of an N-terminal amino acid of a nascent polypeptide. This modification ensures the proper function and intracellular trafficking of certain proteins. Many proteins involved in a wide variety of signaling, including cellular transformation and oncogenesis, are myristoylated.

The investigators reported in the December 22, 2013, online edition of the journal Nature Chemistry that NMT was an essential and chemically tractable target in malaria parasites both in vitro and in vivo, and that selective inhibition of N-myristoylation led to catastrophic and irreversible failure to assemble the inner membrane complex, a critical subcellular organelle in the parasite life cycle.

Senior author Dr. Edward W. Tate, professor of chemistry at Imperial College London (United Kingdom), said, "Finding an enzyme that can be targeted effectively in malaria can be a big challenge. Here, we have shown not only why NMT is essential for a wide range of important processes in the parasite, but also that we can design molecules that stop it from working during infection. It has so many functions that we think blocking it could be effective at preventing long-term disease and transmission, in addition to treating acute malaria. We expect it to work not just on Plasmodium falciparum, the most common malaria parasite, but the other species as well. We need to do some more work in the lab to find the best candidate molecule to take into clinical trials, but hopefully we will be ready to do that within a few years."

Related Links:

Imperial College London



Channels

Genomics/Proteomics

view channel
Image: In mice, mitochondria (green) in healthy (left) and Mfn1-deficient heart muscle cells (center) are organized in a linear arrangement, but the organelles are enlarged and disorganized in Mfn2-deficient cells (right) (Photo courtesy of the Rockefeller Press).

Cell Biologists Find That Certain Mitochondrial Diseases Stem from Coenzyme Q10 Depletion

A team of German cell biologists has linked the development of certain mitochondrial-linked diseases to depletion of the organelles' pool of coenzyme Q10 brought about by mutation in the MFN2 gene, which... Read more

Biochemistry

view channel

Possible New Target Found for Treating Brain Inflammation

Scientists have identified an enzyme that produces a class of inflammatory lipid molecules in the brain. Abnormally high levels of these molecules appear to cause a rare inherited eurodegenerative disorder, and that disorder now may be treatable if researchers can develop suitable drug candidates that suppress this enzyme.... Read more

Lab Technologies

view channel
Image: The FLUOVIEW FVMPE-RS Gantry microscope (Photo courtesy of Olympus).

New Multiphoton Laser Scanning Microscope Configurations Expand Research Potential

Two new configurations of a state-of-the-art multiphoton laser scanning microscope extend the usefulness of the instrument for examining rapidly occurring biological events and for obtaining images from... Read more

Business

view channel

Roche Acquires Signature Diagnostics to Advance Translational Research

Roche (Basel, Switzerland) will advance translational research for next generation sequencing (NGS) diagnostics by leveraging the unique expertise of Signature Diagnostics AG (Potsdam, Germany) in biobanks and development of novel NGS diagnostic assays. Signature Diagnostics is a privately held translational oncology... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.