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.Full text not available in this repository. (Request a copy from the Strathclyde author)
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.
|Keywords:||lead compounds , cathepsin B-like enzyme , Eimeria tenella, Therapeutics. Pharmacology, Infectious Diseases, Pharmacology, Pharmacology (medical)|
|Subjects:||Medicine > Therapeutics. Pharmacology|
|Department:||Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences|
|Depositing user:||Pure Administrator|
|Date Deposited:||08 Dec 2011 09:31|
|Last modified:||27 Apr 2016 18:00|