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

Schaeffer, M., Schroeder, J., Heckeroth, A.R., Noack, S., Gassel, M., Mottram, J.C. , Selzer, P.M. and Coombs, G.H. (2012) Identification of lead compounds targeting the cathepsin B-like enzyme of Eimeria tenella. Antimicrobial Agents and Chemotherapy, 53(3), pp. 1190-1201. (doi:10.1128/AAC.05528-11)

Full text not currently available from Enlighten.

Publisher's URL: http://dx.doi.org/10.1128/AAC.05528-11

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

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Selzer, Dr Paul and Coombs, Professor Graham and Mottram, Professor Jeremy
Authors: Schaeffer, M., Schroeder, J., Heckeroth, A.R., Noack, S., Gassel, M., Mottram, J.C., Selzer, P.M., and Coombs, G.H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Antimicrobial Agents and Chemotherapy
ISSN:0066-4804

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
371793The Wellcome Centre for Molecular Parasitology ( Core Support )J BarryWellcome Trust (WELLCOME)073990/Z/03/BInfection Immunity and Inflammation Life Sciences