title: Parasite prolyl oligopeptidases and the challenge of designing chemotherapeuticals for Chagas disease, leishmaniasis and African trypanosomiasis.
abstract: The trypanosomatids Trypanosoma cruzi, Leishmania spp. and Trypanosoma brucei spp. cause Chagas disease, leishmaniasis and human African trypanosomiasis, respectively. It is estimated that over 10 million people worldwide suffer from these neglected diseases, posing enormous social and economic problems in endemic areas. There are no vaccines to prevent these infections and chemotherapies are not adequate. This picture indicates that new chemotherapeutic agents must be developed to treat these illnesses. For this purpose, understanding the biology of the pathogenic trypanosomatid- host cell interface is fundamental for molecular and functional characterization of virulence factors that may be used as targets for the development of inhibitors to be used for effective chemotherapy. In this context, it is well known that proteases have crucial functions for both metabolism and infectivity of pathogens and are thus potential drug targets. In this regard, prolyl oligopeptidase and oligopeptidase B, both members of the S9 serine protease family, have been shown to play important roles in the interactions of pathogenic protozoa with their mammalian hosts and may thus be considered targets for drug design. This review aims to discuss structural and functional properties of these intriguing enzymes and their potential as targets for the development of drugs against Chagas disease, leishmaniasis and African trypanosomiasis.
authors.affiliation: Pathogen-Host Interface Laboratory, Department of Cell Biology, The University of Brasília, Brasília, Brazil.
authors.forename: I M D
authors.initials: IM
authors.lastname: Bastos
authors.forename: F N
authors.initials: FN
authors.lastname: Motta
authors.forename: P
authors.initials: P
authors.lastname: Grellier
authors.forename: J M
authors.initials: JM
authors.lastname: Santana
mesh_terms: D014355:Chagas Disease / Q000188:drug therapy; D015195:Drug Design; D006801:Humans; D007896:Leishmaniasis / Q000188:drug therapy; D000085822:Prolyl Oligopeptidases; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D014345:Trypanosoma / Q000187:drug effects / Q000201:enzymology; D014352:Trypanosomiasis / Q000188:drug therapy* / Q000469:parasitology; D014353:Trypanosomiasis, African / Q000188:drug therapy
chemical_list: D011480:Protease Inhibitors; D015800:Protozoan Proteins; D014344:Trypanocidal Agents; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases