New approaches for dissecting protease functions to improve probe development and drug discovery (original) (raw)

• Drag, M. & Salvesen, G.S. Emerging principles in protease-based drug discovery. Nat. Rev. Drug Discov. 9, 690–701 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Rawlings, N.D., Barrett, A.J. & Bateman, A. Asparagine peptide lyases: a seventh catalytic type of proteolytic enzymes. J. Biol. Chem. 286, 38321–38328 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Powers, J.C., Asgian, J.L., Ekici, O.D. & James, K.E. Irreversible inhibitors of serine, cysteine, and threonine proteases. Chem. Rev. 102, 4639–4750 (2002).
  Article CAS PubMed Google Scholar
• Johnson, S.L. & Pellecchia, M. Structure- and fragment-based approaches to protease inhibition. Curr. Top. Med. Chem. 6, 317–329 (2006).
  Article CAS PubMed Google Scholar
• Turk, B. Targeting proteases: successes, failures and future prospects. Nat. Rev. Drug Discov. 5, 785–799 (2006).
  Article CAS PubMed Google Scholar
• Shen, A. Allosteric regulation of protease activity by small molecules. Mol. Biosyst. 6, 1431–1443 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Bock, P.E., Panizzi, P. & Verhamme, I.M. Exosites in the substrate specificity of blood coagulation reactions. J. Thromb. Haemost. 5 (suppl. 1), 81–94 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Conus, S. & Simon, H.U. Cathepsins and their involvement in immune responses. Swiss Med. Wkly. 140, w13042 (2010).
  PubMed Google Scholar
• Lupardus, P.J., Shen, A., Bogyo, M. & Garcia, K.C. Small molecule-induced allosteric activation of the Vibrio cholerae RTX cysteine protease domain. Science 322, 265–268 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Bauernfeind, F. et al. Inflammasomes: current understanding and open questions. Cell Mol. Life Sci. 68, 765–783 (2011).
  Article CAS PubMed Google Scholar
• Edgington, L.E. et al. Noninvasive optical imaging of apoptosis by caspase-targeted activity-based probes. Nat. Med. 15, 967–973 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Mason, S.D. & Joyce, J.A. Proteolytic networks in cancer. Trends Cell Biol. 21, 228–237 (2011).
  Article CAS PubMed Google Scholar
• López-Otín, C. & Hunter, T. The regulatory crosstalk between kinases and proteases in cancer. Nat. Rev. Cancer 10, 278–292 (2010).
  Article PubMed CAS Google Scholar
• Smith, D.M., Fraga, H., Reis, C., Kafri, G. & Goldberg, A.L. ATP binds to proteasomal ATPases in pairs with distinct functional effects, implying an ordered reaction cycle. Cell 144, 526–538 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Palermo, C. & Joyce, J.A. Cysteine cathepsin proteases as pharmacological targets in cancer. Trends Pharmacol. Sci. 29, 22–28 (2008).
  Article CAS PubMed Google Scholar
• Overall, C.M. & Kleifeld, O. Tumour microenvironment - opinion: validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy. Nat. Rev. Cancer 6, 227–239 (2006).
  Article CAS PubMed Google Scholar
• Omara-Opyene, A.L. et al. Genetic disruption of the Plasmodium falciparum digestive vacuole plasmepsins demonstrates their functional redundancy. J. Biol. Chem. 279, 54088–54096 (2004).
  Article CAS PubMed Google Scholar
• Deu, E. et al. Functional studies of Plasmodium falciparum dipeptidyl aminopeptidase I using small molecule inhibitors and active site probes. Chem. Biol. 17, 808–819 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Klemba, M., Gluzman, I. & Goldberg, D.E. A Plasmodium falciparum dipeptidyl aminopeptidase I participates in vacuolar hemoglobin degradation. J. Biol. Chem. 279, 43000–43007 (2004).
  Article CAS PubMed Google Scholar
• Dalal, S. & Klemba, M. Roles for two aminopeptidases in vacuolar hemoglobin catabolism in Plasmodium falciparum. J. Biol. Chem. 282, 35978–35987 (2007).
  Article CAS PubMed Google Scholar
• Sadaghiani, A.M., Verhelst, S.H. & Bogyo, M. Tagging and detection strategies for activity-based proteomics. Curr. Opin. Chem. Biol. 11, 20–28 (2007).
  Article CAS PubMed Google Scholar
• Cravatt, B.F., Wright, A.T. & Kozarich, J.W. Activity-based protein profiling: from enzyme chemistry to proteomic chemistry. Annu. Rev. Biochem. 77, 383–414 (2008).
  Article CAS PubMed Google Scholar
• Desmarais, S., Masse, F. & Percival, M.D. Pharmacological inhibitors to identify roles of cathepsin K in cell-based studies: a comparison of available tools. Biol. Chem. 390, 941–948 (2009).
  Article CAS PubMed Google Scholar
• Paulick, M.G. & Bogyo, M. Application of activity-based probes to the study of enzymes involved in cancer progression. Curr. Opin. Genet. Dev. 18, 97–106 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Blum, G. Use of fluorescent imaging to investigate pathological protease activity. Curr. Opin. Drug Discov. Devel. 11, 708–716 (2008).
  CAS PubMed Google Scholar
• Meng, L., Kwok, B.H., Sin, N. & Crews, C.M. Eponemycin exerts its antitumor effect through the inhibition of proteasome function. Cancer Res. 59, 2798–2801 (1999).
  CAS PubMed Google Scholar
• Sin, N. et al. Total synthesis of the potent proteasome inhibitor epoxomicin: a useful tool for understanding proteasome biology. Bioorg. Med. Chem. Lett. 9, 2283–2288 (1999).
  Article CAS PubMed Google Scholar
• Arastu-Kapur, S. et al. Identification of proteases that regulate erythrocyte rupture by the malaria parasite Plasmodium falciparum. Nat. Chem. Biol. 4, 203–213 (2008).
  Article CAS PubMed Google Scholar
• Chang, J.W., Nomura, D.K. & Cravatt, B.F. A potent and selective inhibitor of KIAA1363/AADACL1 that impairs prostate cancer pathogenesis. Chem. Biol. 18, 476–484 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Ahn, K. et al. Discovery and characterization of a highly selective FAAH inhibitor that reduces inflammatory pain. Chem. Biol. 16, 411–420 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Staub, I. & Sieber, S.A. Beta-lactam probes as selective chemical-proteomic tools for the identification and functional characterization of resistance associated enzymes in MRSA. J. Am. Chem. Soc. 131, 6271–6276 (2009).
  Article CAS PubMed Google Scholar
• Adibekian, A. et al. Click-generated triazole ureas as ultrapotent _in vivo_-active serine hydrolase inhibitors. Nat. Chem. Biol. 7, 469–478 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Jain, S., Diefenbach, C., Zain, J. & O'Connor, O.A. Emerging role of carfilzomib in treatment of relapsed and refractory lymphoid neoplasms and multiple myeloma. Core Evid. 6, 43–57 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Hall, C.I. et al. Chemical genetic screen identifies Toxoplasma DJ-1 as a regulator of parasite secretion, attachment, and invasion. Proc. Natl. Acad. Sci. USA 108, 10568–10573 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Chandramohanadas, R. et al. Apicomplexan parasites co-opt host calpains to facilitate their escape from infected cells. Science 324, 794–797 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Gocheva, V. et al. IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Genes Dev. 24, 241–255 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Berger, A.B. et al. Identification of early intermediates of caspase activation using selective inhibitors and activity-based probes. Mol. Cell 23, 509–521 (2006).
  Article CAS PubMed Google Scholar
• Méthot, N. et al. In vivo inhibition of serine protease processing requires a high fractional inhibition of cathepsin C. Mol. Pharmacol. 73, 1857–1865 (2008).
  Article PubMed CAS Google Scholar
• Blum, G., von Degenfeld, G., Merchant, M.J., Blau, H.M. & Bogyo, M. Noninvasive optical imaging of cysteine protease activity using fluorescently quenched activity-based probes. Nat. Chem. Biol. 3, 668–677 (2007).
  Article CAS PubMed Google Scholar
• Blum, G., Weimer, R.M., Edgington, L.E., Adams, W. & Bogyo, M. Comparative assessment of substrates and activity based probes as tools for non-invasive optical imaging of cysteine protease activity. PLoS ONE 4, e6374 (2009).
  Article PubMed PubMed Central CAS Google Scholar
• Hagel, M. et al. Selective irreversible inhibition of a protease by targeting a noncatalytic cysteine. Nat. Chem. Biol. 7, 22–24 (2011).
  Article CAS PubMed Google Scholar
• Blair, J.A. et al. Structure-guided development of affinity probes for tyrosine kinases using chemical genetics. Nat. Chem. Biol. 3, 229–238 (2007).
  Article CAS PubMed Google Scholar
• Agard, N.J., Maltby, D. & Wells, J.A. Inflammatory stimuli regulate caspase substrate profiles. Mol. Cell. Proteomics 9, 880–893 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• auf dem Keller, U. et al. Novel matrix metalloproteinase inhibitor [18F]marimastat-aryltrifluoroborate as a probe for in vivo positron emission tomography imaging in cancer. Cancer Res. 70, 7562–7569 (2010).
  Article CAS PubMed Google Scholar
• Bowyer, P.W., Simon, G.M., Cravatt, B.F. & Bogyo, M. Global profiling of proteolysis during rupture of Plasmodium falciparum from the host erythrocyte. Mol. Cell Proteomics 10, M110.001636 (2011).
  Article PubMed CAS Google Scholar
• Enoksson, M. et al. Identification of proteolytic cleavage sites by quantitative proteomics. J. Proteome Res. 6, 2850–2858 (2007).
  Article CAS PubMed Google Scholar
• Kleifeld, O. et al. Isotopic labeling of terminal amines in complex samples identifies protein N-termini and protease cleavage products. Nat. Biotechnol. 28, 281–288 (2010).
  Article CAS PubMed Google Scholar
• Mahrus, S. et al. Global sequencing of proteolytic cleavage sites in apoptosis by specific labeling of protein N termini. Cell 134, 866–876 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• auf dem Keller, U., Prudova, A., Gioia, M., Butler, G.S. & Overall, C.M. A statistics-based platform for quantitative N-terminome analysis and identification of protease cleavage products. Mol. Cell Proteomics 9, 912–927 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Simon, G.M., Dix, M.M. & Cravatt, B.F. Comparative assessment of large-scale proteomic studies of apoptotic proteolysis. ACS Chem. Biol. 4, 401–408 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Wildes, D. & Wells, J.A. Sampling the N-terminal proteome of human blood. Proc. Natl. Acad. Sci. USA 107, 4561–4566 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Staes, A. et al. Selecting protein N-terminal peptides by combined fractional diagonal chromatography. Nat. Protoc. 6, 1130–1141 (2011).
  Article CAS PubMed Google Scholar
• Prudova, A., auf dem Keller, U., Butler, G.S. & Overall, C.M. Multiplex N-terminome analysis of MMP-2 and MMP-9 substrate degradomes by iTRAQ-TAILS quantitative proteomics. Mol. Cell Proteomics 9, 894–911 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Schilling, O., Barre, O., Huesgen, P.F. & Overall, C.M. Proteome-wide analysis of protein carboxy termini: C terminomics. Nat. Methods 7, 508–511 (2010).
  Article CAS PubMed Google Scholar
• Timmer, J.C. et al. Profiling constitutive proteolytic events in vivo. Biochem. J. 407, 41–48 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Gray, D.C., Mahrus, S. & Wells, J.A. Activation of specific apoptotic caspases with an engineered small-molecule-activated protease. Cell 142, 637–646 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Truebestein, L. et al. Substrate-induced remodeling of the active site regulates human HTRA1 activity. Nat. Struct. Mol. Biol. 18, 386–388 (2011).
  Article CAS PubMed Google Scholar
• Vaidya, S., Velazquez-Delgado, E.M., Abbruzzese, G. & Hardy, J.A. Substrate-induced conformational changes occur in all cleaved forms of caspase-6. J. Mol. Biol. 406, 75–91 (2011).
  Article CAS PubMed Google Scholar
• Hardy, J.A. & Wells, J.A. Dissecting an allosteric switch in caspase-7 using chemical and mutational probes. J. Biol. Chem. 284, 26063–26069 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Scheer, J.M., Romanowski, M.J. & Wells, J.A. A common allosteric site and mechanism in caspases. Proc. Natl. Acad. Sci. USA 103, 7595–7600 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Schneck, J.L. et al. Chemical mechanism of a cysteine protease, cathepsin C, as revealed by integration of both steady-state and pre-steady-state solvent kinetic isotope effects. Biochemistry 47, 8697–8710 (2008).
  Article CAS PubMed Google Scholar
• Patricelli, M.P. et al. In situ kinase profiling reveals functionally relevant properties of native kinases. Chem. Biol. 18, 699–710 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Sheahan, K.L., Cordero, C.L. & Satchell, K.J. Autoprocessing of the Vibrio cholerae RTX toxin by the cysteine protease domain. EMBO J. 26, 2552–2561 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Shen, A. et al. Mechanistic and structural insights into the proteolytic activation of Vibrio cholerae MARTX toxin. Nat. Chem. Biol. 5, 469–478 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Puri, A.W. et al. Rational design of inhibitors and activity-based probes targeting Clostridium difficile virulence factor TcdB. Chem. Biol. 17, 1201–1211 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Falgueyret, J.P. et al. Lysosomotropism of basic cathepsin K inhibitors contributes to increased cellular potencies against off-target cathepsins and reduced functional selectivity. J. Med. Chem. 48, 7535–7543 (2005).
  Article CAS PubMed Google Scholar
• Deu, E., Yang, Z., Wang, F., Klemba, M. & Bogyo, M. Use of activity-based probes to develop high throughput screening assays that can be performed in complex cell extracts. PLoS ONE 5, e11985 (2010).
  Article PubMed PubMed Central CAS Google Scholar
• Thong, B., Pilling, J., Ainscow, E., Beri, R. & Unitt, J. Development and validation of a simple cell-based fluorescence assay for dipeptidyl peptidase 1 (DPP1) activity. J. Biomol. Screen. 16, 36–43 (2011).
  Article CAS PubMed Google Scholar
• Wakata, A. et al. Simultaneous fluorescent monitoring of proteasomal subunit catalysis. J. Am. Chem. Soc. 132, 1578–1582 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Poreba, M. & Drag, M. Current strategies for probing substrate specificity of proteases. Curr. Med. Chem. 17, 3968–3995 (2010).
  Article CAS PubMed Google Scholar
• Whitney, M. et al. Parallel in vivo and in vitro selection using phage display identifies protease-dependent tumor-targeting peptides. J. Biol. Chem. 285, 22532–22541 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Greenbaum, D.C. et al. A role for the protease falcipain 1 in host cell invasion by the human malaria parasite. Science 298, 2002–2006 (2002).
  Article CAS PubMed Google Scholar
• Sadaghiani, A.M. et al. Design, synthesis, and evaluation of in vivo potency and selectivity of epoxysuccinyl-based inhibitors of papain-family cysteine proteases. Chem. Biol. 14, 499–511 (2007).
  Article CAS PubMed Google Scholar
• Albrow, V.E. et al. Development of small molecule inhibitors and probes of human SUMO deconjugating proteases. Chem. Biol. 18, 722–732 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Ponder, E.L. et al. Functional characterization of a SUMO deconjugating protease of Plasmodium falciparum using newly identified small molecule inhibitors. Chem. Biol. 18, 711–721 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Patterson, A.W., Wood, W.J. & Ellman, J.A. Substrate activity screening (SAS): a general procedure for the preparation and screening of a fragment-based non-peptidic protease substrate library for inhibitor discovery. Nat. Protoc. 2, 424–433 (2007).
  Article CAS PubMed Google Scholar
• Patterson, A.W. et al. Identification of selective, nonpeptidic nitrile inhibitors of cathepsin s using the substrate activity screening method. J. Med. Chem. 49, 6298–6307 (2006).
  Article CAS PubMed Google Scholar
• Brak, K., Doyle, P.S., McKerrow, J.H. & Ellman, J.A. Identification of a new class of nonpeptidic inhibitors of cruzain. J. Am. Chem. Soc. 130, 6404–6410 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Brak, K. et al. Nonpeptidic tetrafluorophenoxymethyl ketone cruzain inhibitors as promising new leads for Chagas disease chemotherapy. J. Med. Chem. 53, 1763–1773 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Bachovchin, D.A. et al. Superfamily-wide portrait of serine hydrolase inhibition achieved by library-versus-library screening. Proc. Natl. Acad. Sci. USA 107, 20941–20946 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Ahn, K. et al. Novel mechanistic class of fatty acid amide hydrolase inhibitors with remarkable selectivity. Biochemistry 46, 13019–13030 (2007).
  Article CAS PubMed Google Scholar
• Speers, A.E. & Cravatt, B.F. Profiling enzyme activities in vivo using click chemistry methods. Chem. Biol. 11, 535–546 (2004).
  Article CAS PubMed Google Scholar
• Berkers, C.R. et al. Activity probe for in vivo profiling of the specificity of proteasome inhibitor bortezomib. Nat. Methods 2, 357–362 (2005).
  Article CAS PubMed Google Scholar
• Arastu-Kapur, S. et al. Nonproteasomal targets of the proteasome inhibitors bortezomib and carfilzomib: a link to clinical adverse events. Clin. Cancer Res. 17, 2734–2743 (2011).
  Article CAS PubMed Google Scholar
• Desmarais, S. et al. Effect of cathepsin k inhibitor basicity on in vivo off-target activities. Mol. Pharmacol. 73, 147–156 (2008).
  Article CAS PubMed Google Scholar
• Gauthier, J.Y. et al. The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K. Bioorg. Med. Chem. Lett. 18, 923–928 (2008).
  Article CAS PubMed Google Scholar
• Geurink, P. et al. A peptide hydroxamate library for enrichment of metalloproteinases: towards an affinity-based metalloproteinase profiling protocol. Org. Biomol. Chem. 6, 1244–1250 (2008).
  Article CAS PubMed Google Scholar
• Saghatelian, A., Jessani, N., Joseph, A., Humphrey, M. & Cravatt, B.F. Activity-based probes for the proteomic profiling of metalloproteases. Proc. Natl. Acad. Sci. USA 101, 10000–10005 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Harbut, M.B. et al. Bestatin-based chemical biology strategy reveals distinct roles for malaria M1- and M17-family aminopeptidases. Proc. Natl. Acad. Sci. USA 108, E526–E534 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Sieber, S.A., Niessen, S., Hoover, H.S. & Cravatt, B.F. Proteomic profiling of metalloprotease activities with cocktails of active-site probes. Nat. Chem. Biol. 2, 274–281 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Nakai, R., Salisbury, C.M., Rosen, H. & Cravatt, B.F. Ranking the selectivity of PubChem screening hits by activity-based protein profiling: MMP13 as a case study. Bioorg. Med. Chem. 17, 1101–1108 (2009).
  Article CAS PubMed Google Scholar
• Li, Y.M. et al. Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin 1. Nature 405, 689–694 (2000).
  Article CAS PubMed Google Scholar
• Weerapana, E. et al. Quantitative reactivity profiling predicts functional cysteines in proteomes. Nature 468, 790–795 (2010).
  Article CAS PubMed PubMed Central Google Scholar