Identification of lead compounds targeting the cathepsin B-like enzyme of Eimeria tenella

Marie Schaeffer, Joerg Schroeder, Anja R Heckeroth, Sandra Noack, Michael Gassel, Jeremy C Mottram, Paul M Selzer, Graham H Coombs

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Abstract

Cysteine peptidases have been implicated in the development and pathogenesis of Eimeria. We have identified a single copy cathepsin B-like cysteine peptidase (EtCatB) gene in the genome database of Eimeria tenella. Molecular modeling of the predicted protein suggested that it differs significantly from host enzymes and could be a good drug target. EtCatB was expressed and secreted as a soluble, active, glycosylated mature enzyme from Pichia pastoris. Biochemical characterisation of the recombinant enzyme confirmed that it is cathepsin B-like. Screening of a focused library against the enzyme identified three inhibitors (a nitrile, a thiosemicarbazone and an oxazolon) that can be used as leads for novel drug discovery against Eimeria. The oxazolone scaffold is a novel cysteine peptidase inhibitor, it may thus find widespread use.
Original languageEnglish
JournalAntimicrobial Agents and Chemotherapy
DOIs
Publication statusPublished - 2011

Keywords

  • lead compounds
  • cathepsin B-like enzyme
  • Eimeria tenella

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