[ Back to EurekAlert! ] Public release date: 30-Oct-2007
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Contact: Johanna Dehlinger
press@plos.org
415-624-1202
Public Library of Science

Mexican researchers report intriguing approach to developing treatments for Chagas disease

Mexican researchers highlight a novel approach to discovering drugs for Chagas disease in a laboratory study reported in PLoS Neglected Tropical Diseases.

Chagas disease, caused by the parasite Trypanosoma cruzi, affects about 18 million people in the American continent. Unfortunately, there is no satisfactory treatment for the disease: the existing drugs have severe side effects, require long courses of treatment, and show variable effectiveness.

In the new study, Armando Gómez-Puyou (Universidad Nacional Autonoma de Mexico, Mexico City) and colleagues report results of their search for molecules that could eliminate the parasite. Their work targets an enzyme in the parasite called triosephosphate isomerase.

One of the problems with identifying molecules that attack parasitic enzymes is that most of these enzymes have a counterpart in the human host—and so the molecule may also attack the human enzyme (causing side effects in humans). But triosephosphate isomerase, which has two subunits, holds promise as a possible target because the human form differs from the parasitic form. Armando Gómez-Puyou and colleagues found significance differences in the interface between the two subunits in triosephosphate isomerase from Homo sapiens and that from Trypanosoma cruzi. They therefore searched for molecules that could specifically disrupt this interface in the parasitic form of the enzyme but not the human form.

In their search, they discovered that dithiodianiline (DTDA) is far more effective at inactivating the parasitic form of the enzyme than the human form, and its detrimental effect is due to it perturbing the interface between the two subunits.

By targeting this interface, the researchers say, “it is possible to discover small molecules that selectively thwart the life of the parasite.”

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Citation: Olivares-Illana V, Rodríguez-Romero A, Becker I, Berzunza M, García J, et al. (2007) Perturbation of the Dimer Interface of Triosephosphate Isomerase and its Effect on Trypanosoma cruzi. PLoS Negl Trop Dis 1(1): e01. doi:10.1371/journal.pntd.0000001

MEDIA CONTACT:
Armando Gómez-Puyou
Universidad Nacional Autonoma de Mexico
Instituto de Fisiología Celular
Circuito Exterior, Ciudad Universitaria
Mexico City, D.F. 04510
Mexico
52 55 56225629
52 55 56225630 (fax)
apuyou@ifc.unam.mx

PLEASE MENTION THE OPEN-ACCESS JOURNAL PLoS NEGLECTED TROPICAL DISEASES (www.plosntds.org) AS THE SOURCE FOR THESE ARTICLES AND PROVIDE A LINK TO THE FREELY AVAILABLE TEXT. THANK YOU.

PLoS Neglected Tropical Diseases is an open-access, peer-reviewed journal published weekly by the Public Library of Science (PLoS). Everything published by PLoS Neglected Tropical Diseases is Open Access: freely available for anyone to read, download, redistribute and otherwise use, as long as the authorship is properly attributed.



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