Designing sleeping sickness control.

Control of African trypanosomiasis caused by the protozoan parasite Trypanosoma brucei is an important issue in medicine, veterinary medicine, and agricultural economy. Because vaccine development is unlikely, development of safer and more effective chemotherapeutics is critical. The biosynthetic pathway of glycosylphosphatidylinositol (GPI), which acts as membrane anchors of coat proteins, variant surface glycoproteins, and transferrin receptors, is a validated target of drug development. An article in this issue reports the first chemically synthesized inhibitor of the third mannosyltransferase from the GPI pathway, stimulating further investigation toward practical and useful compounds.