INVESTIGADORES
ALVAREZ Vanina Eder
artículos
Título:
Metacaspases, autophagins and metallocarboxypeptidases: potential new targets for chemotherapy of the trypanosomiases.
Autor/es:
ALVAREZ, V.E.; NIEMIROWICZ, G.T.; CAZZULO, J.J.
Revista:
CURRENT MEDICINAL CHEMISTRY.
Editorial:
BENTHAM SCIENCE PUBL LTD
Referencias:
Lugar: Oak Park; Año: 2013 p. 3069 - 3077
ISSN:
0929-8673
Resumen:
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.