title: Protein farnesyl and N-myristoyl transferases: piggy-back medicinal chemistry targets for the development of antitrypanosomatid and antimalarial therapeutics.
abstract: To accelerate progress in the development of therapeutics for protozoan parasitic diseases, we are studying enzymes active in co- and post-translational protein modification that are already the focus of drug development in other eukaryotic systems. Inhibitors of the protein farnesyltransferases (PFT) are well-established antitumour agents of low cytotoxicity and known pharmokinetic properties, while inhibitors of N-myristoyl transferase show both selectivity and specificity in the treatment of fungal infections. Here, we summarise the current evidence that supports the targeting of these ubiquitous eukaryotic enzymes for drug development against trypanosomatid infections and malaria.
authors.affiliation: Department of Chemistry, University of Washington, Seattle, WA 98195, USA. gelb@chem.washington.edu
authors.forename: Michael H
authors.initials: MH
authors.lastname: Gelb
authors.forename: Wesley C
authors.initials: WC
authors.lastname: Van Voorhis
authors.forename: Frederick S
authors.initials: FS
authors.lastname: Buckner
authors.forename: Kohei
authors.initials: K
authors.lastname: Yokoyama
authors.forename: Richard
authors.initials: R
authors.lastname: Eastman
authors.forename: Elisabeth P
authors.initials: EP
authors.lastname: Carpenter
authors.forename: Chrysoula
authors.initials: C
authors.lastname: Panethymitaki
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Brown
authors.forename: Deborah F
authors.initials: DF
authors.lastname: Smith
mesh_terms: D000217:Acyltransferases / Q000737:chemistry; D019883:Alkyl and Aryl Transferases / Q000737:chemistry; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis*; D002626:Chemistry, Pharmaceutical; D015195:Drug Design; D010961:Plasmodium / Q000201:enzymology; D011487:Protein Conformation; D014344:Trypanocidal Agents / Q000138:chemical synthesis*; D014345:Trypanosoma / Q000201:enzymology
chemical_list: D000962:Antimalarials; D014344:Trypanocidal Agents; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase