Trypanosoma brucei: inhibition of cathepsin L is sufficient to kill bloodstream forms

Steverding, Dietmar, Rushworth, Stuart, Florea, Bogdan I. and Overkleeft, Herman S. (2020) Trypanosoma brucei: inhibition of cathepsin L is sufficient to kill bloodstream forms. Molecular and Biochemical Parasitology, 235. ISSN 0166-6851

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Abstract

The lysosomal cysteine protease activity of Trypanosoma brucei comprises a cathepsin B enzyme (TbCATB) and a cathepsin L enzyme (TbCATL). Inhibition of the cysteine protease activity is lethal to bloodstream-form trypanosomes but it was not entirely clear which of the two enzymes are essential for survival of the parasites. Here we show that the vinyl sulfone compound LU-102 selectively inhibits TbCATL without affecting TbCATB and the proteasomal trypsin-like activity within trypanosomes. Therefore, the trypanocidal activity displayed by LU-102 can be attributed solely to the inhibition of TbCATL demonstrating that this enzyme is essential to the survival of T. brucei.

Item Type:	Article
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	18 Nov 2019 13:30
Last Modified:	25 Oct 2023 01:01
URI:	https://ueaeprints.uea.ac.uk/id/eprint/72990
DOI:	10.1016/j.molbiopara.2019.111246

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