Tackling Trypanosomes

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Science  26 Nov 2004:
Vol. 306, Issue 5701, pp. 1439
DOI: 10.1126/science.306.5701.1439d

Trypanosoma brucei — the protozoan parasite responsible for causing African sleeping sickness in humans and nagana in cattle — expresses on its surface a variable coat protein linked to the membrane via a glycosylphosphatidylinositol (GPI) anchor. Smith et al. demonstrate that the biochemical pathway leading to GPI-linked proteins can be targeted specifically in the parasite. Analogs of intermediates in the GPI pathway were engineered to be able to cross the cell membrane and inhibited GPI synthesis in trypanosomes, while leaving human GPI unaffected. These analogs possessed trypanocidal activity whereas related nonmetabolizable analogs had no such activity. Although these analogs will need to be refined to remain cell-permeable and to survive long enough in serum for bioavailability, they should offer the potential to develop valuable candidate drugs. Currently, there are more than 30,000 cases of African sleeping sickness annually, and the therapies available are often toxic and troublesome to administer. — SMH

EMBO J. 10.1038/sj.emboj.7600456 (2004).

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