Murine and human cathepsin B exhibit similar properties: possible implications for drug discovery

Abstract Validation of drug targets and subsequent preclinical studies are usually carried out on animal disease models, with mouse being the most commonly used. However, results from mouse models cannot always be directly related to human disease. Major discrepancies between the properties of murine and human variants were observed during the evaluation of compounds targeting cathepsins S and K. It is important, therefore, to know whether similar differences exist between murine and human cathepsin B. Thus, both enzymes were expressed and biochemically characterized. The enzymes exhibited similar biochemical properties, indicating that cathepsin B transgenic mouse models could be useful for studying its role in human pathologies.

[1]  K. Kato,et al.  Purification and Characterization of Microsomal and Lysosomal β‐Glucuronidase from Rat Liver by Use of Immunoaffinity Chromatography , 1976 .

[2]  T. Chambers,et al.  Recent developments in cathepsin K inhibitor design. , 2005, Current opinion in drug discovery & development.

[3]  A. Sands,et al.  Knockouts model the 100 best-selling drugs—will they model the next 100? , 2003, Nature Reviews Drug Discovery.

[4]  Bonnie F. Sloane,et al.  Transcription of human cathepsin B is mediated by Sp1 and Ets family factors in glioma. , 2000, DNA and cell biology.

[5]  Y. Ru,et al.  Potent and Selective Inhibition of Human Cathepsin K Leads to Inhibition of Bone Resorption In Vivo in a Nonhuman Primate , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[6]  B. Turk Targeting proteases: successes, failures and future prospects , 2006, Nature Reviews Drug Discovery.

[7]  O. Vasiljeva,et al.  Tumor cell-derived and macrophage-derived cathepsin B promotes progression and lung metastasis of mammary cancer. , 2006, Cancer research.

[8]  A. Barrett,et al.  Human kidney cathepsins B and L. Characterization and potential role in degradation of glomerular basement membrane. , 1988, The Biochemical journal.

[9]  David W. Anderson,et al.  SP500263, a novel SERM, blocks osteoclastogenesis in a human bone cell model: role of IL-6 and GM-CSF. , 2003, Cytokine.

[10]  Mouse Genome Sequencing Consortium Initial sequencing and comparative analysis of the mouse genome , 2002, Nature.

[11]  Mario Huerta,et al.  Identification of patterns in biological sequences at the ALGGEN server: PROMO and MALGEN , 2003, Nucleic Acids Res..

[12]  O. Vasiljeva,et al.  Reduced tumour cell proliferation and delayed development of high-grade mammary carcinomas in cathepsin B-deficient mice , 2008, Oncogene.

[13]  T. Moreau,et al.  Photometric or fluorometric assay of cathepsin B, L and H and papain using substrates with an aminotrifluoromethylcoumarin leaving group. , 1991, Biochimica et biophysica acta.

[14]  O. Vasiljeva,et al.  Emerging roles of cysteine cathepsins in disease and their potential as drug targets. , 2007, Current pharmaceutical design.

[15]  C. Tsou,et al.  Determination of the rate constant of enzyme modification by measuring the substrate reaction in the presence of the modifier. , 1982, Biochemistry.

[16]  D. Turk,et al.  Lysosomal cysteine proteases: facts and opportunities , 2001, The EMBO journal.

[17]  H. Kirschke,et al.  The specificity of bovine spleen cathepsin S. A comparison with rat liver cathepsins L and B. , 1989, The Biochemical journal.

[18]  M. James,et al.  Effects of disease-modifying anti-rheumatic drugs (DMARDs) on the activities of rheumatoid arthritis-associated cathepsins K and S , 2007, Biological chemistry.

[19]  Wen Jiang,et al.  Discovery and SAR studies of a novel series of noncovalent cathepsin S inhibitors. , 2005, Bioorganic & medicinal chemistry letters.

[20]  W. Delano The PyMOL Molecular Graphics System , 2002 .

[21]  J. Thompson,et al.  The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. , 1997, Nucleic acids research.

[22]  J. Kos,et al.  Inhibitory properties of cystatin F and its localization in U937 promonocyte cells , 2005, The FEBS journal.

[23]  K. Hara,et al.  Rat epidermal cathepsin B: Purification and characterization of proteolytic properties toward filaggrin and synthetic substrates , 1995 .

[24]  V. Turk,et al.  Autocatalytic processing of recombinant human procathepsin B is a bimolecular process , 1999, FEBS letters.

[25]  V. Turk,et al.  Glycosaminoglycans Facilitate Procathepsin B Activation through Disruption of Propeptide-Mature Enzyme Interactions* , 2007, Journal of Biological Chemistry.

[26]  C. Walsh,et al.  The behavior and significance of slow-binding enzyme inhibitors. , 2006, Advances in enzymology and related areas of molecular biology.

[27]  D. Hanahan,et al.  Distinct roles for cysteine cathepsin genes in multistage tumorigenesis. , 2006, Genes & development.

[28]  Y. Ru,et al.  Azepanone-based inhibitors of human and rat cathepsin K. , 2001, Journal of medicinal chemistry.

[29]  V. Turk,et al.  The preparation of catalytically active human cathepsin B from its precursor expressed in Escherichia coli in the form of inclusion bodies. , 1995, European journal of biochemistry.

[30]  Bonnie F. Sloane,et al.  Cysteine cathepsins: multifunctional enzymes in cancer , 2006, Nature Reviews Cancer.

[31]  Bonnie F. Sloane,et al.  Molecular Regulation of Human Cathepsin B: Implication in Pathologies , 2003, Biological chemistry.

[32]  B. Turk,et al.  Cysteine proteases: destruction ability versus immunomodulation capacity in immune cells , 2007, Biological chemistry.

[33]  A. Sali,et al.  Comparative protein structure modeling of genes and genomes. , 2000, Annual review of biophysics and biomolecular structure.

[34]  M. Murata,et al.  Novel epoxysuccinyl peptides Selective inhibitors of cathepsin B, in vitro , 1991, FEBS letters.

[35]  K. Brix,et al.  Cysteine cathepsins: cellular roadmap to different functions. , 2008, Biochimie.