Design, synthesis, and evaluation of aza-peptide Michael acceptors as selective and potent inhibitors of caspases-2, -3, -6, -7, -8, -9, and -10

Journal of Medicinal Chemistry

Volumn 49, Issue 19, 2006, Pages 5728-5749

  Ekici, Özlem Doǧan ^a   Li, Zhao Zhao ^a   Campbell, Amy J ^a   James, Karen Ellis ^a   Asgian, Juliana L ^a   Mikolajczyk, Jowita ^b   Salvesen, Guy S ^b   Ganesan, Rajkumar ^c   Jelakovic, Stjepan ^c   Grütter, Markus G ^c   Powers, James C ^a  

^a GEORGIA INSTITUTE OF TECHNOLOGY   (United States)

^b BURNHAM INSTITUTE   (United States)

^c UNIVERSITY OF ZURICH   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

2 N (N BENZYLOXYCARBONYLASPARTYLGLUTAMYLVALYL) 1 N CARBOXYMETHYL 1 N (3 DI 1 NAPHTHYLCARBAMOYLACRYLOYL)HYDRAZINE; CALPAIN; CASPASE; CASPASE 10; CASPASE 2; CASPASE 3; CASPASE 6; CASPASE 7; CASPASE 8; CASPASE 9; CASPASE INHIBITOR; CATHEPSIN B; CYSTEINE PROTEINASE; HETEROCYCLIC COMPOUND; PAPAIN; UNCLASSIFIED DRUG;

ARTICLE; COMPLEX FORMATION; CROSS REACTION; CRYSTAL STRUCTURE; DRUG DESIGN; DRUG POTENCY; DRUG SCREENING; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; ENZYME INHIBITOR INTERACTION; ENZYME SPECIFICITY; MICHAEL ADDITION; NONHUMAN;

AZA COMPOUNDS; CASPASE 10; CASPASE 2; CASPASE 3; CASPASE 6; CASPASE 7; CASPASE 9; CASPASES; CRYSTALLOGRAPHY, X-RAY; KINETICS; MODELS, MOLECULAR; OLIGOPEPTIDES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33748859423     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0601405     Document Type: Article

References (48)

1. Barrett, A. J.; Rawlings, N. D. Evolutionary Lines of Cysteine Peptidases. Biol. Chem. 2001, 382, 727-733.
2. Barrett, A. J.; Rawlings, N. D.; O'Brien, E. A. The MEROPS Database as a Protease Information System. J. Struct. Biol. 2001, 134, 95-102.
3. Denault, J. B.; Salvesen, G. S. Caspases: Keys in the Ignition of Cell Death. Chem. Rev. 2002, 102, 4489-4500.
4. Yuan, J.; Yankner, B. A. Apoptosis in the Nervous System. Nature 2000, 407, 802-809.
5. Talanian, R. V.; Brady, K. D.; Cryns, V. L. Caspases as Targets for Antiinflammatory and Anti-Apoptotic Drug Discovery. J. Med. Chem. 2000, 43, 3351-3371.
6. Los, M.; Burek, C. J.; Stroh, C.; Benedyk, K.; Hug, H.; Mackiewicz, A. Anticancer Drugs of Tomorrow: Apoptotic Pathways as Targets for Drug Design. Drug Discovery Today 2003, 8, 67-77.
7. Salgado, J.; Garcia-Saez, A. J.; Malet, G.; Mingarro, I.; Perez-Paya, E. Peptides in Apoptosis Research. J. Pept. Sci. 2002, 8, 543-560.
8. Friedlander, R. M. Apoptosis and Caspases in Neurodegenerative Diseases. N. Engl. J. Med. 2003, 348, 1365-1375.
9. Powers, J. C.; Asgian, J. L.; Ekici, O. D.; James, K. E. Irreversible Inhibitors of Serine, Cysteine, and Threonine Proteases. Chem. Rev. 2002, 102, 4639-4750.
10. Nicholson, D. W. Caspase Structure, Proteolytic Substrates, and Function During Apoptotic Cell Death. Cell Death Differ. 1999, 6, 1028-1042.
11. Rozman-Pungercar, J.; Kopitar-Jerala, N.; Bogyo, M.; Turk, D.; Vasiljeva, O.; Stefe, I.; Vandenabeele, P.; Bromme, D.; Puizdar, V.; Fonovic, M.; Trstenjak-Prebanda, M.; Dolenc, I.; Turk, V.; Turk, B. Inhibition of Papain-Like Cysteine Proteases and Legumain by Caspase-Specific Inhibitors: When Reaction Mechanism Is More Important Than Specificity. Cell Death Differ. 2003, 10, 881-888.
12. Leist, M.; Jaattela, M. Triggering of Apoptosis by Cathepsins. Cell Death Differ. 2001, 8, 324-326.
13. Turk, B.; Stoka, V.; Rozman-Pungercar, J.; Cirman, T.; Droga-Mazovec, G.; Oreic, K.; Turk, V. Apoptotic Pathways: Involvement of Lysosomal Proteases. Biol. Chem. 2002, 383, 1035-1044.
14. Barrett, A. J.; Kembhavi, A. A.; Brown, M. A.; Kirschke, H.; Knight, C. G.; Tama, M.; Hanada, K. L-Trans-Epoxysuccinyl-Leucylamido-(4-Guanidino)Butane (E-64) and Its Analogues as Inhibitors of Cysteine Proteinases Including Cathepsin B, H, and L. Biochem. J. 1982, 201, 189-198.
15. Hanzlik, R. P.; Thompson, S. A. Vinylogous Amino Acid Esters: A New Class of Inactivators for Thiol Proteases. J. Med. Chem. 1984, 27, 711-712.
16. Thompson, S. A.; Andrews, P. R.; Hanzlik, R. P. Carboxyl-Modified Amino Acids and Peptides as Protease Inhibitors. J. Med. Chem. 1986, 29, 104-111.
17. Palmer, J. T.; Rasnick, D.; Klaus, J. L. Irreversible Cysteine Protease Inhibitors Containing Vinyl Groups Conjugated to Electron Withdrawing Groups. US Patent 6,287,840, 2001.
18. Matthews, D. A.; Dragovich, P. S.; Webber, S. E.; Fuhrman, S. A.; Patick, A. K.; Zalman, L. S.; Hendrickson, T. F.; Love, R. A.; Prins, T. J.; Marakovits, J. T.; Zhou, R.; Tikhe, J.; Ford, C. E.; Meador, J. W.; Ferre, R. A.; Brown, E. L.; Binford, S. L.; Brothers, M. A.; DeLisle, D. M.; Worland, S. T. Structure-Assisted Design of Mechanism-Based Irreversible Inhibitors of Human Rhinovirus 3C Protease with Potent Antiviral Activity against Multiple Rhinovirus Serotypes. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 11000-11007.
19. Patick, A. K.; Binford, S. L.; Brothers, M. A.; Jackson, R. L.; Ford, C. E.; Diem, M. D.; Maldonado, F.; Dragovich, P. S.; Zhou, R.; Prins, T. J.; Fuhrman, S. A.; Meador, J. W.; Zalman, L. S.; Matthews, D. A.; Worland, S. T. In Vitro Antiviral Activity of AG7088, a Potent Inhibitor of Human Rhinovirus 3C Protease. Antimicrob. Agents Chemother. 1999, 43, 2444-2450.
20. Zhang, K. E.; Hee, B.; Lee, C. A.; Liang, B.; Potts, B. C. Liquid Chromatography-Mass Spectrometry and Liquid Chromatography-NMR Characterization of in Vitro Metabolites of a Potent and Irreversible Peptidomimetic Inhibitor of Rhinovirus 3C Protease. Drug Metab. Dispos. 2001, 29, 729-734.
21. Dragovich, P. S.; Prins, T. J.; Zhou, R.; Brown, E. L.; Maldonado, F. C.; Fuhrman, S. A.; Zalman, L. S.; Tuntland, T.; Lee, C. A.; Patick, A. K.; Matthews, D. A.; Hendrickson, T. F.; Kosa, M. B.; Liu, B.; Batugo, M. R.; Gleeson, J. P.; Sakata, S. K.; Chen, L.; Guzman, M. C.; Meador, J. W., 3rd; Ferre, R. A.; Worland, S. T. Structure-Based Design, Synthesis, and Biological Evaluation of Irreversible Human Rhinovirus 3C Protease Inhibitors. 6. Structure-Activity Studies of Orally Bioavailable, 2-Pyridone-Containing Peptidomimetics. J. Med. Chem. 2002, 45, 1607-1623.
22. Sirois, S.; Wei, D. Q.; Du, Q.; Chou, K. C. Virtual Screening for SARS-CoV Protease Based on KZ7088 Pharmacophore Points. J. Chem. Inf. Comput. Sci. 2004, 44, 1111-1122.
23. Ekici, O. D.; Gotz, M. G.; James, K. E.; Li, Z. Z.; Rukamp, B. J.; Asgian, J. L.; Caffrey, C. R.; Hansell, E.; Dvorak, J.; McKerrow, J. H.; Potempa, J.; Travis, J.; Mikolajczyk, J.; Salvesen, G. S.; Powers, J. C. Aza-Peptide Michael Acceptors: A New Class of Inhibitors Specific for Caspases and Other Clan CD Cysteine Proteases. J. Med. Chem. 2004, 47, 1889-1892.
24. Choong, I. C.; Lew, W.; Lee, D.; Pham, P.; Burdett, M. T.; Lam, J. W.; Wiesmann, C.; Luong, T. N.; Fahr, B.; DeLano, W. L.; McDowell, R. S.; Allen, D. A.; Erlanson, D. A.; Gordon, E. M.; O'Brien, T. Identification of Potent and Selective Small-Molecule Inhibitors of Caspase-3 through the Use of Extended Tethering and Structure-Based Drug Design. J. Med. Chem. 2002, 45, 5005-5022.
25. O'Brien, T., Lee, D. Prospects for Caspase Inhibitors. Mini Rev. Med. Chem. 2004, 4, 153-165.
26. Becker, J. W.; Rotonda, J.; Soisson, S. M.; Aspiotis, R.; Bayly, C.; Francoeur, S.; Gallant, M.; Garcia-Calvo, M.; Giroux, A.; Grimm, E.; Han, Y.; McKay, D.; Nicholson, D. W.; Peterson, E.; Renaud, J.; Roy, S.; Thornberry, N.; Zamboni, R. Reducing the Peptidyl Features of Caspase-3 Inhibitors: A Structural Analysis. J. Med. Chem. 2004, 47, 2466-2474.
27. Stennicke, H. R.; Renatus, M.; Meldal, M.; Salvesen, G. S. Internally Quenched Fluorescent Peptide Substrates Disclose the Subsite Preferences of Human Caspases 1, 3, 6, 7 and 8. Biochem. J. 2000, 350, 563-568.
28. Thornberry, N. A. Caspases: Key Mediators of Apoptosis. Chem. Biol. 1998, 5, R97-R103.
29. Thornberry, N. A.; Rano, T. A.; Peterson, E. P.; Rasper, D. M.; Timkey, T.; Garcia-Calvo, M.; Houtzager, V. M.; Nordstrom, P. A.; Roy, S.; Vaillancourt, J. P.; Chapman, K. T.; Nicholson, D. W. A Combinatorial Approach Defines Specificities of Members of the Caspase Family and Granzyme B. Functional Relationships Established for Key Mediators of Apoptosis. J. Biol. Chem. 1997, 272, 17907-17911.
30. Talanian, R. V.; Quinlan, C.; Trautz, S.; Hackett, M. C.; Mankovitich, J. A.; Banach, D.; Ghayur, T.; Brady, K. D.; Wong, W. W. Substrate Specificities of Caspase Family Proteases. J. Biol. Chem. 1997, 272, 9677-9682.
31. Blanchard, H.; Donepudi, M.; Tschopp, M.; Kodandapani, L.; Wu, J. C.; Grutter, M. G. Caspase-8 Specificity Probed at Subsite S(4): Crystal Structure of the Caspase-8-Z-Devd-CHO Complex. J. Mol. Biol. 2000, 302, 9-16.
32. Wei, Y.; Fox, T.; Chambers, S. P.; Sintchak, J.; Coll, J. T.; Golec, J. M.; Swenson, L.; Wilson, K. P.; Charifson, P. S. The Structures of Caspases-1, -3, -7 and -8 Reveal the Basis for Substrate and Inhibitor Selectivity. Chem. Biol. 2000, 7, 423-432.
33. Yang, W.; Guastella, J.; Huang, J. C.; Wang, Y.; Zhang, L.; Xue, D.; Tran, M.; Woodward, R.; Kasibhatla, S.; Tseng, B.; Drewe, J.; Cai, S. X. MX1013, a Dipeptide Caspase Inhibitor with Potent in Vivo Antiapoptotic Activity. Br. J. Pharmacol. 2003, 140, 402-412.
34. Freidig, A. P.; Verhaar, H. J. M.; Hermens, J. L. M. Comparing the Potency of Chemicals with Multiple Modes of Action in Aquatic Toxicology: Acute Toxicity Due to Narcosis Versus Reactive Toxicity of Acrylic Compounds. Environ. Sci. Technol. 1999, 33, 3038-3043.
35. Rotonda, J.; Nicholson, D. W.; Fazil, K. M.; Gallant, M.; Gareau, Y.; Labelle, M.; Peterson, E. P.; Rasper, D. M.; Ruel, R.; Vaillancourt, J. P.; Thornberry, N. A.; Becker, J. W. The Three-Dimensional Structure of Apopain/CPP32, a Key Mediator of Apoptosis. Nature Struct. Biol. 1996, 3, 619-625.
36. Watt, W.; Koeplinger, K. A.; Mildner, A. M.; Heinrikson, R. L.; Tomasselli, A. G.; Watenpaugh, K. D. The Atomic-Resolution Structure of Human Caspase-8, a Key Activator of Apoptosis. Structure Fold. Des. 1999, 7, 1135-1143.
37. Mittl, P. R.; Marco, S. D.; Krebs, J. F.; Bai, X.; Karanewsky, D. S.; Priestle, J. P.; Tomaselli, K. J.; Grütter, M. G. Structure of Recombinant Human CPP32 in Complex with the Tetrapeptide Acetyl-Asp-Val-Ala-Asp Fluoromethyl Ketone. J. Biol. Chem. 1997, 272, 6539-6547.
38. Blanchard, H.; Kodandapani, L.; Mittl, P. R.; Marco, S. D.; Krebs, J. F.; Wu, J. C.; Tomaselli, K. J.; Grutter, M. G. The Three-Dimensional Structure of Caspase-8: An Initiator Enzyme in Apoptosis. Structure Fold. Des. 1999, 7, 1125-1133.
39. Xu, G.; Cirilli, M.; Huang, Y.; Rich, R. L.; Myszka, D. G.; Wu, H. Covalent Inhibition Revealed by the Crystal Structure of the Caspase-8/P35 Complex. Nature 2001, 410, 494-497.
40. Batchelor, M. J.; Mellor, J. M. The Use of Dichloromaleic and Bromomaleic Anhydrides in the Synthesis of Lactones by the Intramolecular Diels-Alder Reaction. J. Chem. Soc., Perkin Trans. 1 1989, 985-995.
41. Stennicke, H. R.; Salvesen, G. S. Caspases: Preparation and Characterization. Methods 1999, 17, 313-319.
42. Tian, W. X.; Tsou, C. L. Determination of the Rate Constant of Enzyme Modification by Measuring the Substrate Reaction in the Presence of the Modifier. Biochemistry 1982, 21, 1028-1032.
43. Leslie, A. G. W. Mosflm User Guide Version 6.2.3. Joint CCP4 and ESF-EAMCB Newsletter on Protein Crystallography, No. 26, 1992.
44. Anonymous The CCP4 Suite: Programs for Protein Crystallography Collaborative Computational Project, Number 4. Acta Crystallogr. D Biol. Crystallogr. 1994, 50, 760-763.
45. Kabsch, W. Automatic Indexing of Rotation Diffraction Patterns. J. Appl. Crystallogr. 1988, 21, 67-72.
46. Kabsch, W. Evaluation of Single-Crystal X-ray Diffraction Data from a Position-Sensitive Detector. J. Appl. Crystallogr. 1988, 21, 916-924.
47. Brunger, A. T.; Adams, P. D.; Clore, G. M.; DeLano, W. L.; Gros, P.; Grosse-Kunstleve, R. W.; Jiang, J. S.; Kuszewski, J.; Nilges, M.; Pannu, N. S.; Read, R. J.; Rice, L. M.; Simonson, T.; Warren, G. L. Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination. Acta Crystallogr. D Biol. Crystallogr. 1998, 54, 905-921.
48. Garcia-Calvo, M.; Peterson, E. P.; Leiting, B.; Ruel, R.; Nicholson, D. W.; Thornberry, N. A. Inhibition of Human Caspases by Peptide-Based and Macromolecular Inhibitors. J. Biol. Chem. 1998, 273, 32608-32613.