During the last decade, de novo
drug discovery approaches have come into focus due to the increased number of parasite pathogen genomes sequenced and the subsequent availability of genome-scale functional datasets. In order to prioritize target
proteins, these approaches consider traits commonly thought to be desirable in a
drug target, including essentiality, druggability (whether
drug-like molecules are likely to interact with the target), assayability, importance in lifecycle stages of the pathogen relevant to human health, and specificity (i.e. the target is absent from, or substantially different in, the host).
Proteases from protozoan parasites have become popular
drug targets since these
enzymes accomplish both housekeeping tasks common to many eukaryotes as well as functions highly specific to the parasite life style. Trypanosoma cruzi, the parasitic flagellate, agent of
Chagas Disease, contains several
cysteine,
serine,
threonine and metallo
proteinases. This review will deal with peculiar families described in this parasite. Among them, two eukaryote homologues of the
carboxypeptidases Taq are promising targets due to their particular phylogenetic distribution. Also absent in metazoans, metacaspases are essential
peptidases playing important roles in cell growth, death and differentiation of trypanosomatids. Finally, autophagins are involved in the regulation of a conserved degradative pathway, the autophagy pathway, and result important for parasite survival under nutritional stress conditions and differentiation. Although so far there are no specific inhibitors for these families, the increasing knowledge of their biochemical properties, including substrate specificity, crystal structure, and
biological functions, is an essential step towards the development of inhibitors.