Farnesyl Diphosphate Synthase as a Target for Parasitic Disease

Bisphosphonates, drugs used to treat bone resorption, have been shown to have an antiparasitic effect. In humans, they act by targeting farnesyl diphosphate synthase to lower the levels of protein prenylation. Our work is focused in tailoring nitrogen-containing bisphosphonates to the parasitic enzymes of the isoprenoid pathway, minimizing the drug inhibitory effect in the host. We are using mutational analysis, enzymatic assays, isothermal calorimetry and X-ray crystallography to give the structural basis of specificity of the compounds. As part of the project we have tailored pharmacophores to increase specificity for the T. cruzi and  Leishmania major farnesyl diphosphate synthase vs that of humans.