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Hot Paper: Cure for Chagas' disease a step closer
30 July 2007
Researchers in the UK and Brazil have developed a method to make molecules that will help to develop a cure for a debilitating parasitic infection.

Trypanosoma cruzi |
Chagas' disease is a frequently fatal condition, common in South and Central America. It is caused by the single-celled parasite Trypanosoma cruzi. The drugs available to treat the disease are often ineffective, expensive, and highly toxic. A team of chemists lead by Robert Field at the University of East Anglia, Norwich, UK, and Ivone Carvalho at the University of São Paulo, Brazil, have been working towards a cure for this distressing disease. Field talks more about his work in the short interview below.
1. Could you explain the significance of your article to the non-specialist?
The South American trypanosome, Trypanosoma cruzi is the etiologic agent of Chagas' disease, a debilitating and often fatal condition prevalent in South and Central American populations. Currently around 18 million people are infected by the parasite, with a further 120 million at risk. Approximately 50,000 people die each year, but additionally the economic burden on populations incapacitated by the infection are tremendous. The drugs currently available for treatment of Chagas´ disease are limited and generally ineffective; there is a clear need for new therapeutics. We have explored the synthesis of glycopeptide fragments of parasite-specific cell surface mucin glycoproteins that are essential for host cell invasion, and hence parasite reproduction. This has involved a combination of chemical and enzymatic methods to produce glycopeptides with which to investigate enzymes that are thought to be central to the infection process - step towards drug target identification and lead generation.
2. What motivated you to undertake this work?
This is one of those problems that present numerous challenges from a research perspective, but it also has the potential to underpin drug discovery for neglected diseases of the developing world. The project has enabled us to forge closer links with researchers from Brazil, a country where T. cruzi infection is still prevalent.
3. Where do you see this work developing in the future? What challenges might there be?
Trypanosoma cruzi must invade human cells to reproduce. In order to do that, it must first bind to mammalian cells, of course. If we can understand how the surface of the parasite is involved in mammalian cell adhesion and invasion, there is scope to develop inhibitors of these processes. That is, we would not be looking for lead compounds that kill the parasite directly, merely that stop it binding to host cells. If the parasites hang around long enough in the bloodstream, the host immune response will kill them anyway.
4. How long have you been involved in this area of research?
We have worked in this area, on-and-off for about 10 years. However, synthetic carbohydrate chemistry has improved so much in that time, we are now able to make molecules that we couldn't have considered making when we first began.
Related Links
Chemical and chemoenzymatic synthesis of glycosyl-amino acids and glycopeptides related to Trypanosoma cruzi mucins
Vanessa Leiria Campo, Ivone Carvalho, Sarah Allman, Benjamin G. Davis and Robert A. Field, Org. Biomol. Chem., 2007, 5, 2645
DOI: 10.1039/b707772f
Cure for Chagas' disease a step closer
Combining chemical and enzymatic approaches brings promise of a cure for a debilitating parasitic disease.
