Atomistic insights into the inhibition of cysteine proteases: First QM/MM calculations clarifying the regiospecificity and the inhibition potency of epoxide- and aziridine-based inhibitors

Journal of Physical Chemistry B

Volumn 112, Issue 17, 2008, Pages 5458-5469

  Mladenovic, Milena ^a   Junold, Konstantin ^a   Fink, Reinhold F ^a   Thiel, Walter ^b   Schirmeister, Tanja ^a   Engels, Bernd ^a  

^a UNIVERSITY OF WÜRZBURG   (Germany)

^b MAX PLANCK INSTITUT FÜR KOHLENFORSCHUNG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ARSENIC COMPOUNDS; BIOCHEMISTRY; CHEMOTHERAPY; CLARIFICATION; DRUG DELIVERY; DRUG DOSAGE; DYNAMICS; ENZYME ACTIVITY; ENZYMES; FLOW INTERACTIONS; FOOD ADDITIVES; MOLECULAR DYNAMICS; MOLECULAR MECHANICS; QUANTUM CHEMISTRY; REACTION KINETICS;

AMERICAN CHEMICAL SOCIETY (ACS); AZIRIDINE; AZIRIDINES; BASIC PRINCIPLES; BUILDING BLOCKS; CLASSICAL MOLECULAR DYNAMICS (CMD); COMPUTATIONAL RESULTS; CYSTEINE PROTEASES; DRUG TARGETING; EXPERIMENTAL DATA; HYBRID APPROACHES; INHIBITION PROCESSES; MODE OF ACTION; QM/MM CALCULATIONS; QUANTUM MECHANICAL/MOLECULAR MECHANICAL (QM/MM); RATIONAL DESIGN; REACTION BARRIERS; REGIOSPECIFICITY; STEREOSPECIFICITY; STRUCTURAL ARRANGEMENTS; STRUCTURE-ACTIVITY RELATIONSHIP (SAR); SUBSTITUTION PATTERNS; TWO-STEP MODEL; X RAY STRUCTURES;

ENZYME INHIBITION;

EID: 46949103330     PISSN: 15206106     EISSN: None     Source Type: Journal    
DOI: 10.1021/jp711287c     Document Type: Article

References (88)

1. Chen, Z. P.; Zhu, X. L.; Fu, G. D.; Kang, E. T.; Neoh, K. G. Macromolecules 2005, 38, 7187.
2. Carlier, P. R. Angew. Chem., Int. Ed. 2004, 43, 2602.
3. Padva, A.; Murohree, S. ARKIVOC 2006, 3, 6.
4. Aziridines and Epoxides in Organic Synthesis; Yudin, A. K., Ed.; Wiley-VCH: Weinheim, Germany, 2006.
5. (a) Powers, J. C.; Asgain, J. L.; Ekici, O. D.; James, K. E. Chem. Rev. 2002, 102, 4639.
6. (b) Schirmeister, T.; Klockow, A. Mini Rev. Med. Chem. 2003, 3, 585.
7. Kim, T. S.; Tasker, A. S. Curr. Top. Med. Chem. 2006, 6, 355.
8. Roberts, R. Drug News Perspect. 2005, 18, 605.
9. Gocheva, V.; Joyce, J. A. Cell Cycle 2007, 6, 60.
10. Ook, V. Y. BioDrugs 2006, 20, 105.
11. Rosenthal, P. J. Int. J. Parasitol. 2004, 34, 1489.
12. Caffrey, C. R.; Scory, S.; Steverding, D. Curr. Drug Targets 2000, 1, 155.
13. Jose Cazzulo, J.; Stoka, V.; Turk, V. Curr. Pharm. Des. 2001, 7, 1143.
14. Eilon, G. F.; Gu, J.; Slater, L. M.; Hara, K.; Jacobs, J. W. Cancer Chemother. Pharmacol. 2000, 45, 183.
15. (a) Vicik, R.; Hoerr, V.; Glaser, M.; Schultheis, M.; Hansell, E.; McKerrow, J. H.; Holzgrabe, U.; Caffrey, C. R.; Ponte-Sucre, A.; Moll, H.; Stich, A.; Schirmeister, T. Bioorg. Med. Chem. Lett. 2006, 16, 2753.
16. (b) Ponte-Sucre, A.; Vicik, R.; Schultheis, M.; Schirmeister, T.; Moll, H. Antimicrob. Agents Chemother. 2006 50, 2439.
17. (c) Schulz, F.; Gelhaus, C.; Degel, B.; Vicik, R.; Heppner, S.; Breuning, A.; Leippe, M.; Gut, J.; Rosenthal, P. J.; Schirmeister, T. ChemMedChem 2007, 2, 1214.
18. (a) Gelhaus, C.; Vicik, R.; Hilgenfeld, R.; Schmidt, C. L.; Leippe, M.; Schirmeister, T. Biol. Chem. 2004, 385, 435.
19. (b) Gelhaus, C.; Vicik, R.; Schirmeister, T.; Leippe, M. Biol. Chem. 2005, 386, 499.
20. (c) Vicik, R.; Busemann, M.; Gelhaus, C.; Stiefl, N.; Scheiber, J.; Schmitz, W.; Schulz, F.; Mladenovic, M.; Engels, B.; Leippe, M.; Baumann, K.; Schirmeister, T. ChemMedChem 2006, 1, 1126.
21. Hanada, K.; Tamai, M.; Morimoto, S.; Adachi, T.; Ohmura, S.; Sawada, J.; Tanaka, I. Agric. Biol. Chem. 1978, 42, 537.
22. Yamamoto, A.; Tomoo, K.; Matsugi, K.; Hara, T.; In, Y.; Murata, M.; Kitamura, K.; Ishida, T. Biochim. Biophys. Acta 2002, 1597, 244.
23. Fujishima, A.; Imai, Y.; Nomura, T.; Fujisawa, Y.; Yamamoto, Y.; Sugawara, T. FEBS Lett. 1997, 407, 47.
24. Zhao, B.; Janson, C. A.; Amegadzie, B. Y.; D'Alessio, K.; Griffin, C.; Hanning, C. R.; Jones, C.; Kurdyla, J.; McQueney, M.; Qiu, X.; Smith, W. W.; Abdel-Meguid, S. S. Nat. Struct. Biol. 1997, 4, 109.
25. Yamamoto, D.; Matsumoto, K.; Ohishi, H.; Ishida, T.; Inoue, M.; Kitamura, K.; Mizuno, H. J. Biol. Chem. 1991, 266, 14771.
26. Varughese, K. I.; Su, Y.; Cromwell, D.; Hasnain, S.; Xuong, N. Biochemistry 1992, 31, 5172.
27. Kim, M.; Yamamoto, D.; Matsumoto, K.; Inoue, M.; Ishida, T.; Mizuno, H.; Sumia, S.; Kitamura, K. Biochem. J. 1992, 287, 797.
28. Vicik, R.; Helten, H.; Schirmeister, T.; Engels, B. ChemMedChem 2006, 3, 1021.
29. Meara, J. P.; Rich, D. H. Bioorg. Med. Chem. Lett. 1995, 5, 2277.
30. Bihovsky, R.; Powers, J. C.; Kam, C. M.; Walton, R.; Loew, R. C. J. Enzyme Inhib. 1993, 7, 15.
31. (a) Martichonok, V.; Plouffe, C.; Storer, A. C.; Ménard, R.; Jones, J. B. J. Med. Chem. 1995, 38, 3078.
32. (b) Schirmeister, T. Arch. Pharm. Pharm. Med. Chem. 1995, 329, 239.
33. Watanabe, D.; Yamamoto, A.; Tomoo, K.; Matsumoto, K.; Murata, M.; Kitamura, K.; Ishida, T. J. Mol. Biol. 2006, 362, 979.
34. Meara, J. P.; Rich, D. H. J. Med. Chem. 1996, 39, 3357.
35. Bihovsky, R. J. Org. Chem. 1992, 57, 1029.
36. (a) Ma, S.; Lakshmi, S. D.-K.; Gao, J. J. Am. Chem. Soc. 2007, 129, 13633.
37. (b) Strajbl, M.; Florian, J.; Warshel, A. J. Phys. Chem. B 2001, 105, 4471.
38. (c) Harrison, M. J.; Burton, N. A.; Hillier, I. H. J. Am. Chem. Soc. 1997, 119, 12285.
39. Helten, H.; Schirmeister, T.; Engels, B. J. Phys. Chem. A 2004, 108, 7691.
40. Helten, H.; Schirmeister, T.; Engels, B. J. Org. Chem. 2005, 70, 233.
41. (a) Aqvist, J.; Warshel, A. Chem. Rev. 1993, 93, 2523.
42. (b) Gao, J. In Reviews in Computational Chemistry; Ipkowitz, K. B., Boyd, D. B., Eds.; VCH: Weinheim, Germany, 1995; Vol. 7, p 119.
43. (c) Mordasini, T. Z.; Thiel, W. Chimia 1998, 52, 288.
44. (d) Warshel, A.; Levitt, M. J. Mol. Biol. 1976, 103, 227.
45. (e) Cavalli, A.; Carloni, P.; Recanatini, M. Chem. Rev. 2006, 106, 3497.
46. (f) Senn, H. M.; Thiel, W. Top. Curr. Chem. 2007, 268, 173.
47. For some further reviews see: (a) Monard, G.; Merz, K. M., Jr. Acc. Chem. Res. 1999, 32, 904.
48. (b) Gao, J.; Truhlar, D. G. Annu. Rev. Phys. Chem. 2002, 53, 467.
49. (c) Field, M. J. J. Comput. Chem. 2002, 23, 48.
50. (d) Monard, G.; Prat-Resina, X.; Gonzalez-Lafont, A.; Lluch, J. M. Int. J. Quantum Chem. 2003, 93, 229.
51. (e) Ridder, L.; Mulholland, A. Curr. Top. Med. Chem. 2003, 3, 1241.
52. Bakowies, D.; Thiel, W. J. Phys. Chem. 1996, 100, 10580.
53. (a) Field, M. J.; Bash, P. A.; Karplus, M. J. J. Comput. Chem. 1990, 11, 700.
54. (b) Amara, P.; Field, M. J. J. Theor. Chem. Acc. 2003, 109, 43.
55. (c) Reuter, N.; Dejaegere, A.; Maigret, B.; Karplus, M. J. Phys. Chem. A 2000, 104, 1720.
56. (d) Singh, U. C.; Kollman, P. A. J. Comput. Chem. 1986, 7, 718.
57. (e) Derat, E.; Bouquant, J.; Humbel, S. THEOCHEM 2003, 632, 61.
58. (f) deVries, A. H.; Sherwood, P.; Collins, S. J.; Rigby, A. M.; Rigutto, M.; Kramer, G. J. J. Phys. Chem. B 1999, 103, 6133.
59. (a) MacKerell, A. D., Jr.; Bashford, D.; Bellot, M.; Dunbrack, R. L., Jr.; Evanseck, J. D.; Field, M. J.; Fischer, S.; Gao, J.; Guo, H.; Ha, S.; Joseph-McCarthy, D.; Kuchnir, L.; Kuczera, K.; Lau, F. T. K.; Mattos, C.; Michnick, S.; Ngo, T.; Nguyen, D. T.; Prodhom, B.; Reiher, W. E., III; Roux, B.; Schlenkrich, M.; Smith, J. C.; Stote, R.; Straub, J.; Watanabe, M.; Wiorkiewicz-Kuczera, J.; Yin, D.; Karplus, M. J. Phys. Chem. B 1998, 102, 3586.
60. (b) Brooks, B. R.; Bruccoleri, R. E.; Olafson, B. D.; States, D. J.; Swaminathan, S.; Karplus, M. J. Comput. Chem. 1983, 4, 187.
61. (c) MacKerell, A. D., Jr.; Brooks, B. R.; Brooks, C. L., III; Nilsson, L.; Roux, B.; Won, Y.; Karplus, M. In The Encyclopedia of Computational Chemistry; Schleyer, P. v. R., Allinger, N. L., Kollman, P. A., Clark, T., Gasteiger, J., Schaefer, H. F., III, Eds.; John Wiley & Sons: Chichester, U.K., 1998; Vol. 1 pp 271-277.
62. Sherwood, P.; de Vries, A. H.; Guest, M. F.; Schreckenbach, G.; Catlow, C. R. A.; French, S. A.; Sokol, A. A.; Bromley, S. T.; Thiel, W.; Turner, A. J.; Billeter, S.; Terstegen, F.; Thiel, S.; Kendrick, J.; Rogers, S. C.; Casci, J.; Watson, M.; King, F.; Karlsen, E.; Sjovoll, M.; Fahmi, A.; Schafer, A.; Lennartz, C. J. Mol. Struct. (THEOCHEM) 2003, 632, 1-28.
63. Böcker, S.; Ehrig, M.; Eichkorn, K.; Elliott, S.; Haase, F.; Häser, M.; Horn, H.; Huber, C.; Huniar, U.; Kattannek, M.; Kölmel, C.; Kollwitz, M.; Ochsenfeld, C.; Öhm, H., Schäfer, A.; Schneider, U.; Treutler, O.; von Arnim, M.; Weigend, F.; Weis, P.; Weiss, H. TURBOMOLE, (since 1988), version 5.6; University of Karlsruhe: Karlsruhe, Germany.
64. Smith, W.; Forester, T. J. Mol. Graphics 1996, 14, 136.
65. Billeterm, S. R.; Turner, A. J.; Thiel, W. Phys. Chem. Chem. Phys. 2000, 2, 2177.
66. Berendsen, H. J. C.; Postma, J. P. M.; van Gunsteren, W. F.; DiNola, A.; Haak, J. R. J. Chem. Phys. 1984, 81, 3684.
67. (a) Verlet, L. Phys. Rev. 1967 159, 98.
68. (b) Hockney, R. W. Methods Comput. Phys. 1970, 9, 136.
69. Please note that the His residue in the active site is denoted as His159 for the papain numbering, whereas His199 is used within the cathepsin B numbering. In the Introduction the papain numbering was employed since more investigations were performed for this enzyme. For the present study cathepsin B was used since more appropriate X-ray structures exist. Therefore, the cathepsin B numbering is used in sections 2-4.
70. (a) Vahtras, O.; Almlöf, J.; Feyereisen, M. W. Chem. Phys. Lett 1993, 213, 514.
71. (b) Eichkorn, K.; Treutler, O.; Öhm, H.; Häser, M.; Ahlrichs, R. Chem. Phys. Lett 1995, 242, 652.
72. (a) Becke, A. D. Phys. Rev. A. 1988, 38, 3098.
73. (b) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785.
74. Schäfer, A.; Huber, C.; Ahlrichs, R. J. Chem. Phys. 1997, 100, 5829.
75. Becke, A. D. J. Chem. Phys. 1993, 98, 5648.
76. Adam, W.; Bottke, N.; Engels, B.; Krebs, O. J. Am. Chem. Soc. 2001, 123, 5542.
77. Schlund, S.; Mladenovic, M.; Basilio Janke, E. M.; Engels, B.; Weisz, K. J. Am. Chem. Soc. 2005, 127, 16151.
78. Hupp, T.; Sturm, C.; Basilio Janke, E. M.; Perez Cabre, M.; Weisz, K.; Engels, B. J. Phys. Chem. 2005, 109, 1703.
79. Engels, B.; Schoeneboom, J. C.; Munster, A. F.; Groetsch, S.; Christi, M. J. Am. Chem. Soc. 2002, 124, 287.
80. Suter, H. U.; Pless, V.; Ernzerhof, M.; Engels, B. Chem. Phys. Lett. 1994, 230, 398.
81. Suter, H. U.; Engels, B. J. Chem. Phys. 1994, 100, 2936.
82. Engels, B. Theor. Chim. Acta 1993, 86, 429.
83. Schmittel, M.; Steffen, J. P.; Engels, B.; Lennartz, C.; Hanrath, M. Angew. Chem., Int. Ed. 1998, 37, 2371.
84. Engels, B.; Peyerimhoff, S. D. J. Phys. Chem. 1989, 93, 4462.
85. Engels, B.; Hanrath, M.; Lennartz, C. Comput. Chem. 2001, 25, 15.
86. Musch, P. W.; Engels, B. J. Am. Chem. Soc. 2001, 123, 5557.
87. Carlier, P. R.; Deora, N.; Crawford, T. D. J. Org. Chem. 2006, 71, 1592.
88. Mladenovic, M.; Schirmeister, T.; Thiel, S.; Thiel, W.; Engels, B. ChemMedChem 2007, 2, 120.