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Thematic review series: lipid posttranslational modifications Fighting parasitic disease by blocking protein farnesylation Eastman RT; Buckner FS; Yokoyama K; Gelb MH; Van Voorhis WCJ Lipid Res 2006[Feb]; 47 (2): 233-40Protein farnesylation is a form of posttranslational modification that occurs in most, if not all, eukaryotic cells. Inhibitors of protein farnesyltransferase (PFTIs) have been developed as anticancer chemotherapeutic agents. Using the knowledge gained from the development of PFTIs for the treatment of cancer, researchers are currently investigating the use of PFTIs for the treatment of eukaryotic pathogens. This "piggy-back" approach not only accelerates the development of a chemotherapeutic agent for protozoan pathogens but is also a means of mitigating the costs associated with de novo drug design. PFTIs have already been shown to be efficacious in the treatment of eukaryotic pathogens in animal models, including both Trypanosoma brucei, the causative agent of African sleeping sickness, and Plasmodium falciparum, one of the causative agents of malaria. Here, current evidence and progress are summarized that support the targeting of protein farnesyltransferase for the treatment of parasitic diseases.|Animals[MESH]|Enzyme Inhibitors/chemistry/pharmacology/therapeutic use[MESH]|Eukaryota/drug effects/metabolism[MESH]|Farnesyltranstransferase/*antagonists & inhibitors/metabolism[MESH]|Humans[MESH]|Molecular Structure[MESH]|Parasitic Diseases/*drug therapy/parasitology[MESH]|Protein Prenylation/*drug effects[MESH]|Protozoan Infections/drug therapy/parasitology[MESH] |
