Article Dans Une Revue Antimicrobial Agents and Chemotherapy Année : 2012

Identification of Lead Compounds Targeting the Cathepsin B-Like Enzyme of Eimeria tenella

Marie Schaeffer
Joerg Schroeder
  • Fonction : Auteur
Anja Heckeroth
  • Fonction : Auteur
Sandra Noack
  • Fonction : Auteur
Michael Gassel
  • Fonction : Auteur
Jeremy Mottram
  • Fonction : Auteur
Paul Selzer
  • Fonction : Auteur
Graham Coombs
  • Fonction : Auteur

Résumé

ABSTRACT Cysteine peptidases have been implicated in the development and pathogenesis of Eimeria . We have identified a single-copy cathepsin B-like cysteine peptidase gene in the genome database of Eimeria tenella ( EtCatB ). 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 characterization 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 oxazolone) 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.

Dates et versions

hal-04707721 , version 1 (24-09-2024)

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Citer

Marie Schaeffer, Joerg Schroeder, Anja Heckeroth, Sandra Noack, Michael Gassel, et al.. Identification of Lead Compounds Targeting the Cathepsin B-Like Enzyme of Eimeria tenella. Antimicrobial Agents and Chemotherapy, 2012, 56 (3), pp.1190-1201. ⟨10.1128/AAC.05528-11⟩. ⟨hal-04707721⟩
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