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New Drug Shown to Be Effective Against Malaria Using Synchrotron Light

By BiotechDaily International staff writers
Posted on 04 Aug 2014
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Image: In this image, the drug CD27 completely covers the minor groove of the DNA complex (Photo courtesy of the Universitat Politècnica de Catalunya).
Image: In this image, the drug CD27 completely covers the minor groove of the DNA complex (Photo courtesy of the Universitat Politècnica de Catalunya).
Spanish and Scottish investigators have shown that a new drug is an effective option in the battle against malaria.

An international group of researchers led by Dr. Lourdes Campos from the department of chemical engineering at the Universitat Politècnica de Catalunya•BarcelonaTech (UPC; Spain) has proven that the CD27 drug can be an effective option against malaria. Researchers came to this conclusion after studying the three-dimensional (3D) crystalline structure of the complex of DNA with the drug.

The CD27 drug is a complex synthesized by researchers led by Dr. Christophe Dardonville at the Instituto de Química Médica of the Spanish National Research Council’s/(IQM-CSIC) in Madrid. “CD27 is chemically related to diamidines--molecules with two amidines--and has previously been used with success in other Trypanosoma species that produce the ‘sleeping sickness’ in Africa and Chagas disease in South America,” said Dr. Campos.

The findings show how the CD27 drug completely covers the minor groove of the DNA, preventing the typical development of the parasite and causing its destruction. This research helps to better understand this range of compounds and may substantially contribute to the development of new, more effective drugs against malaria.

Once the samples of the drug were validated by Harry P. De Koning, a researcher at the University of Glasgow (Scotland, UK), they were sent to the UPC research group in crystallography, structure, and function of biologic macromolecules (MACROM), led by Dr. Campos. For over one year, the group has been working to obtain the crystalline structure of DNA.

Obtaining a DNA crystal is a multiparametric process and requires different variables; furthermore, before obtaining a DNA crystal with the drug, several tests under different conditions are required. The crystal must present a very high molecule order in the crystalline network, as this is crucial for determining the tridimensional structure of the complex. “Obtaining a good crystal is a long and hard task and requires the collaboration of groups from different disciplines. With the help of synchrotrons like the ALBA, science can make a big step forward in comparison with the methods that were available 20 years ago,” said Dr. Campos.

In the next phase, researchers studied the crystals of the complex of DNA with the drug using x-rays at the XALOC macromolecular diffraction beamline of the ALBA synchrotron (www.cells.es), located in Cerdanyola del Vallès, Spain. X-rays, when they pass through the crystal and diffract, project images of spots which, after mathematic analysis, can solve the tridimensional structure of a molecule. When MACROM researchers solved the 3D structure, they identified the details of CD27’s structure, enabling the drug to recognize the regions of DNA covering the minor groove and preventing the development of the parasite. At the same time, these studies contribute to a rational design of new drugs, bearing in mind the molecular interactions caused by CD27.

The research findings have been confirmed and deposited at the Protein Data Bank, a 3D database of proteins and nucleic acids, and published June 2014 in the journal Acta Crystallographica D. The drug is patent-free and can be produced by any pharmaceutical company interested in its development.

ALBA is the Spanish synchrotron light source. ALBA, meaning “Sunrise” in Catalan and in Spanish, is a synchrotron radiation facility. It is a complex of electron accelerators that produce synchrotron light, which allows the atomic structure of matter to be visualized and its properties to be studied. ALBA has been in operation since May 2012 and has seven experimental beamlines. This scientific infrastructure produces 5,000 hours of beamtime per year and is available for academics and the industrial sector and serves more than 1,000 researchers every year.

Related Links:

Universitat Politècnica de Catalunya•BarcelonaTech
University of Glasgow
ALBA synchrotron

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