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

Tools

Schaeffer, Marie and Schroeder, Joerg and Heckeroth, Anja R and Noack, Sandra and Gassel, Michael and Mottram, Jeremy C and Selzer, Paul M and Coombs, Graham H (2011) Identification of lead compounds targeting the cathepsin B-like enzyme of Eimeria tenella. Antimicrobial Agents and Chemotherapy. (https://doi.org/10.1128/AAC.05528-11)

Full text not available in this repository.Request a copy

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.

CORE (COnnecting REpositories)