Cyclic Nucleotide Signaling Mechanisms in Trypanosomes: Possible Targets for Therapeutic Agents

A phylogenetic tree depicting the four different phosphodies-terase (PDE) families in trypanosomes andL. major. The four phosphodi-esterase (PDE) families are conserved across trypanosome and leishmania species. Sequence differences—particularly in the regulatory domains—can be substantial not only across genera but also within species. Thus, development of “broad spectrum” regulatory domain inhibitors might prove fruitless. On the other hand, catalytic site inhibitors designed against one PDE family are more likely to be effective across species and genera. Tbr, T. brucei; Tcr, T. cruzi; Lmj, L. major. The nucleotide sequences were aligned using CLUSTALW and the phylogenetic tree was built using the PHYLIP program.