Update on relevant trypanosome peptidases: Validated targets and future challenges

Biochim Biophys Acta Proteins Proteom. 2021 Feb;1869(2):140577. doi: 10.1016/j.bbapap.2020.140577. Epub 2020 Nov 30.

Abstract

Trypanosoma cruzi, the agent of the American Trypanosomiasis, Chagas disease, and Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, the agents of Sleeping sickness (Human African Trypanosomiasis, HAT), as well as Trypanosoma brucei brucei, the agent of the cattle disease nagana, contain cysteine, serine, threonine, aspartyl and metallo peptidases. The most abundant among these enzymes are the cysteine proteases from the Clan CA, the Cathepsin L-like cruzipain and rhodesain, and the Cathepsin B-like enzymes, which have essential roles in the parasites and thus are potential targets for chemotherapy. In addition, several other proteases, present in one or both parasites, have been characterized, and some of them are also promising candidates for the developing of new drugs. Recently, new inhibitors, with good selectivity for the parasite proteasomes, have been described and are very promising as lead compounds for the development of new therapies for these neglected diseases. This article is part of a Special Issue entitled: "Play and interplay of proteases in health and disease".

Keywords: Antiparasitic agent; Chagas disease; Inhibitor; Peptidase; Protease; Sleeping sickness; Target.

Publication types

  • Review

MeSH terms

  • Animals
  • Cathepsin B / genetics
  • Cathepsin B / isolation & purification
  • Cattle
  • Cysteine Endopeptidases / chemistry
  • Cysteine Endopeptidases / therapeutic use
  • Cysteine Proteases / genetics
  • Cysteine Proteinase Inhibitors / therapeutic use
  • Humans
  • Peptide Hydrolases / genetics*
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / therapeutic use
  • Trypanosoma brucei brucei / enzymology
  • Trypanosoma brucei brucei / genetics*
  • Trypanosoma brucei brucei / pathogenicity
  • Trypanosoma cruzi / enzymology
  • Trypanosoma cruzi / genetics*
  • Trypanosoma cruzi / pathogenicity
  • Trypanosomiasis, African / enzymology
  • Trypanosomiasis, African / genetics*
  • Trypanosomiasis, African / parasitology

Substances

  • Cysteine Proteinase Inhibitors
  • Protozoan Proteins
  • Cysteine Proteases
  • Peptide Hydrolases
  • Cysteine Endopeptidases
  • rhodesain
  • Cathepsin B
  • cruzipain