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

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.
LanguageEnglish
JournalAntimicrobial Agents and Chemotherapy
DOIs
Publication statusPublished - 2011

Fingerprint

Eimeria tenella
Cathepsin B
Cysteine
Eimeria
Enzymes
Peptide Hydrolases
Oxazolone
Thiosemicarbazones
Nitriles
Pichia
Drug Discovery
Protease Inhibitors
Libraries
Genome
Databases
Lead
Pharmaceutical Preparations
Genes
Proteins

Keywords

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

Cite this

Schaeffer, Marie ; Schroeder, Joerg ; Heckeroth, Anja R ; Noack, Sandra ; Gassel, Michael ; Mottram, Jeremy C ; Selzer, Paul M ; Coombs, Graham H. / Identification of lead compounds targeting the cathepsin B-like enzyme of Eimeria tenella. In: Antimicrobial Agents and Chemotherapy. 2011.
@article{75a7c0ded232448ca8881020a5562296,
title = "Identification of lead compounds targeting the cathepsin B-like enzyme of Eimeria tenella",
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.",
keywords = "lead compounds , cathepsin B-like enzyme , Eimeria tenella",
author = "Marie Schaeffer and Joerg Schroeder and Heckeroth, {Anja R} and Sandra Noack and Michael Gassel and Mottram, {Jeremy C} and Selzer, {Paul M} and Coombs, {Graham H}",
year = "2011",
doi = "10.1128/AAC.05528-11",
language = "English",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",

}

Identification of lead compounds targeting the cathepsin B-like enzyme of Eimeria tenella. / Schaeffer, Marie; Schroeder, Joerg; Heckeroth, Anja R; Noack, Sandra; Gassel, Michael; Mottram, Jeremy C; Selzer, Paul M; Coombs, Graham H.

In: Antimicrobial Agents and Chemotherapy, 2011.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Identification of lead compounds targeting the cathepsin B-like enzyme of Eimeria tenella

AU - Schaeffer, Marie

AU - Schroeder, Joerg

AU - Heckeroth, Anja R

AU - Noack, Sandra

AU - Gassel, Michael

AU - Mottram, Jeremy C

AU - Selzer, Paul M

AU - Coombs, Graham H

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

KW - lead compounds

KW - cathepsin B-like enzyme

KW - Eimeria tenella

UR - http://www.scopus.com/inward/record.url?scp=84857173873&partnerID=8YFLogxK

U2 - 10.1128/AAC.05528-11

DO - 10.1128/AAC.05528-11

M3 - Article

JO - Antimicrobial Agents and Chemotherapy

T2 - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

ER -