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

Dietmar Steverding, Stuart Rushworth, Bogdan I. Florea, Herman S. Overkleeft

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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.
Original languageEnglish
Article number111246
Number of pages4
JournalMolecular and Biochemical Parasitology
Volume235
Early online date16 Nov 2019
DOIs
Publication statusPublished - Jan 2020

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