Trypanosomatidae Peptidases: A Target for Drugs Development

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Abstract:

In most organisms around 2% of the genes code for peptidases being this number only surmounted by the genes that code for transcriptional factors. This ubiquitous presence is almost unequaled and has for long fascinated biochemists. Although peptidases have been classified in four mechanistic classes (aspartic-, cysteine-, serine- and metallo-peptidases), the more recent MEROPS database recognizes 42 evolutionary distinct peptidase structures corresponding to 42 different families. As peptidases are involved in several physiological processes they are an obvious target for the development of therapeutic agents to treat infectious disease. The Trypanosomatidae family includes etiologic agents for human and veterinary diseases, such as Trypanosoma cruzi, Leishmania spp. and the African trypanosomes that are responsible for the Chagas disease, for a wide spectrum of clinical manifestations known as leishmaniasis, and for the “sleeping sickness”, respectively. These microorganisms present a complex life cycle that includes dimorphic developmental stages in distinct hosts and by extension show nutritional adaptation. This review covers the recent advances in the biochemical characterization of trypanosomatid proteolytic enzymes and that of specific inhibitors to block their hydrolytic activity, in accordance to the peptidases potential role as target to the treatment of the aforementioned illnesses.





Keywords: Leishmania; Trypanosoma; Trypanosomatidae family; chagas disease; eishmaniasis; peptidases; peptidases inhibitors; proteolysis; sleeping sickness; trypanosomatidae peptidases

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/157340807779815468

Affiliations: Instituto de Microbiologia Prof. Paulo de Goes (IMPPG), CCS, Bl. I, UFRJ, Rio de Janeiro, 21941-590, Brazil.

Publication date: February 1, 2007

More about this publication?
  • Current Enzyme Inhibition aims to publish all the latest and outstanding developments in enzyme inhibition studies with regards to the mechanisms of inhibitory processes of enzymes, recognition of active sites, and the discovery of agonists and antagonists, leading to the design and development of new drugs of significant therapeutic value. Each issue contains a series of timely, in-depth reviews written by leaders in the field, covering a range of enzymes that can be exploited for drug development. Current Enzyme Inhibition is an essential journal for every pharmaceutical and medicinal chemist who wishes to have up-to-date knowledge about each and every development in the study of enzyme inhibition.

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