Using the electrostatic field effect to design a new class of inhibitors for cysteine proteases

Journal of the American Chemical Society

Volumn 119, Issue 18, 1997, Pages 4285-4291

  Conroy, Jeffrey L ^a   Sanders, Tanya C ^a   Seto, Christopher T ^a  

^a BROWN UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYSTEINE PROTEINASE;

ARTICLE; COMPETITIVE INHIBITION; ENZYME ACTIVE SITE; ENZYME INHIBITION; EQUILIBRIUM CONSTANT; HYDROGEN BOND; MOLECULAR INTERACTION; NONHUMAN; PROTEINASE INHIBITION; REACTION ANALYSIS;

EID: 0030909327     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja9641867     Document Type: Article

References (52)

1. (a) Winstein, S.; Shatavsky, M.; Norton, C.; Woodward, R. B. J. Am. Chem. Soc. 1955, 77, 4183.
2. (b) Winstein, S.; Shatavsky, M. J. Am. Chem. Soc. 1956, 78, 592.
3. (c) For a recent review, see: Bowden, K.; Grubbs, E. J. Chem. Soc. Rev. 1996, 25, 171.
4. Lowry, T. H.; Richardson, K. S. Mechanism and Theory in Organic Chemistry, 3rd ed.; Harper and Row: New York, 1987.
5. (a) Roberts, J. D.; Moreland, W. T., Jr. J. Am. Chem. Soc. 1953, 75, 2167.
6. (b) Holtz, H. D.; Stock, L. M. J. Am. Chem. Soc. 1964, 86, 5188.
7. Chen, C.-T.; Siegel, J. S. J. Am. Chem. Soc. 1994, 116, 5959.
8. (a) For an example taken from synthetic organic chemistry, see: Boeckman, R. K., Jr.; Connell, B. T. J. Am. Chem. Soc. 1995, 117, 12368.
9. (b) For a discussion of field and resonance effects in benzoxazinone inhibitors of human leukocyte elastase, see: Krantz, A.; Spencer, R. W.; Tam, T. F.; Liak, T. J.; Copp, L. J.; Thomas, E. M.; Rafferty, S. P. J. Med. Chem. 1990, 33, 464.
10. Van Noorden, C. F.; Smith, R. E.; Rasnick, D. J. Rheumatol. 1988, 115, 1525.
11. Prous, J. R., Ed. Drugs Future 1986, 11, 927-943.
12. (a) Liotta, L. A.; Steeg, P. S.; Stetler-Stevenson, J. G. Cell 1991, 64, 327.
13. (b) Baricos, W. H.; Zhou, Y.; Mason, R. W.; Barrett, A. J. Biochem. J. 1988, 252, 301.
14. (a) Hanzlik, R. P.; Jacober, S. P.; Zygmunt, J. Biochim. Biophys. Acta 1991, 1073, 33.
15. (b) Cheng, H.; Keitz, P.; Jones, J. B. J. Org. Chem. 1994, 59, 7671.
16. Hanzlik, R. P.; Zygmunt, J.; Moon, J. B. Biochem. Biophys. Acta 1990, 1035, 62.
17. Hu, L.-Y.; Abeles, R. H. Arch. Biochem. Biophys. 1990, 281, 271.
18. Ando, R.; Morinaka, Y.; Tokuyama, H.; Isaka, M.; Nakamura, E. J. Am. Chem. Soc. 1993, 115, 1174.
19. (a) Moon, J. B., Coleman, R. S.; Hanzlik, R. P. J. Am. Chem. Soc. 1986, 108, 1350.
20. (b) Brisson, J.-R.; Carey, P. R.; Storer, A. C. J. Biol. Chem. 1986, 261, 9087.
21. (c) Gamcsik, M. P.; Malthous, J. P. G.; Primrose, W. U.; Mackenzie, N. E.; Boyd, A. S. F.; Russell, R. A.; Scott, A. I. J. Am. Chem. Soc. 1983, 105, 6324.
22. (d) Liang, T.-C; Abeles, R. H. Arch. Biochem. Biophys. 1987, 252, 626.
23. (a) Hanzlik, R. P.; Jacober, S. P.; Zygmunt, J. Biochim. Biophys. Acta 1991, 1073, 33.
24. (b) Berti, P. J.; Faerman, C. H.; Storer, A. C. Biochemistry 1991, 30, 1394.
25. Bendall, M. R.; Cartwright, I. L.; Clart, P. I.; Lowe, G.; Nurse, D. Eur. J. Biochem. 1977, 79, 201.
26. Geneste, P.; Durand, R.; Hugon, I.; Reminiac, C. J. Org. Chem. 1979, 44, 1971.
27. Das, G.; Thornton, E. R. J. Am. Chem. Soc. 1993, 115, 1302.
28. Burkey, T. J.; Fahey, R. C. J. Org. Chem. 1985, 50, 1304.
29. (a) Allinger, N. L.; Tribgle, M. T.; Miller, M. A. Tetrahedron 1972, 28, 1173.
30. (b) Gung, B. W.; Wolf, M. A.; Mareska, D. A.; Karipides, A. J. Org. Chem. 1994, 59, 4899.
31. (20) Transannular anomeric interactions have been used previously to explain reaction rates and axial selectivities for addition of nucleophiles to 4-heterocyclohexanones. It is possible that these types of interactions also stabilize the hemithioketal that results from nucleophilic addition of a thiol to these ketones. (a) Cieplak, A. S. J. Am. Chem. Soc. 1981, 103, 4540. (b) Cieplak, A. S. J. Am. Chem. Soc. 1989, 111, 8447 and references therein.
32. Transannular anomeric interactions have been used previously to explain reaction rates and axial selectivities for addition of nucleophiles to 4-heterocyclohexanones. It is possible that these types of interactions also stabilize the hemithioketal that results from nucleophilic addition of a thiol to these ketones. (a) Cieplak, A. S. J. Am. Chem. Soc. 1981, 103, 4540. (b) Cieplak, A. S. J. Am. Chem. Soc. 1989, 111, 8447 and references therein.
33. (a) Imperiali, B.; Abeles, R. H. Biochemistry 1986, 25, 3760.
34. (b) Brady, K.; Abeles, R. H. Biochemistry 1990, 29, 7608.
35. (c) Govardhan, C. P.; Abeles, R. H. Arch. Biochem. Biophys. 1990, 280, 137.
36. (a) Smith, R. A.; Copp, L. J.; Donnelly, S. L.; Spencer, R. W.; Krantz, A. Biochemistry 1988, 27, 6568.
37. (b) Peptide monofluoromethyl ketones have been shown to be selective irreversible inhibitors of cysteine proteases: Rasnick, D. Anal. Biochem. 1985, 149, 461.
38. (c) Rauber, P.; Angliker, H.; Walker, B.; Shaw, E. Biochem. J. 1986, 239, 633.
39. Burkey, T. J.; Fahey, R. C. J. Am. Chem. Soc. 1983, 105, 868.
40. (a) Wiberg, K. B.; Morgan, K. M.; Maltz, H. J. Am. Chem. Soc. 1994, 116, 11067.
41. (b) Van Luppen, J. J.; Lepoivre, J. A.; Dommissee, R. A.; Alderweireldt, F. C. Org. Magn. Reson. 1979, 12, 399.
42. Sanders, E. G.; Jencks, W. P. J. Am. Chem. Soc. 1968, 90, 6154.
43. Dowd, P.; Choi, S.-C. Tetrahedron 1991, 47, 4847.
44. Shioiri, T.; Ninomiya, K.; Yamada, S. J. Am. Chem. Soc. 1972, 94, 6203.
45. (a) Carpino, L. A.; Sadat-Aalaee, D.; Chao, H. G.; DeSelms, R. H. J. Am. Chem. Soc. 1990, 112, 9651.
46. (b) Carpino, L. A.; Mansour, E. M. E.; Sadat-Aalaee, D. J. Org. Chem. 1991, 56, 2611.
47. Corey, E. J.; Erickson, B. W. J. Org. Chem. 1971, 36, 3553.
48. Enzyme assays were performed according to the procedures of ref 11. None of these compounds showed evidence of slow-binding inhibition. Lineweaver-Burk plots are available in the Supporting Information.
49. (a) Swain, C. G.; Lupton, E. C., Jr. J. Am. Chem. Soc, 1968, 90, 4328.
50. (b) Swain, C. G.; Unger, S. H.; Rosenquist, N. R.; Swain, M. S. J. Am. Chem. Soc. 1983, 105, 492.
51. RSH,app and the resonance substituent constant R (correlation coefficient = 0.41)
52. For a similar analysis involving inhibitors of cathepsin B, see: ref 22a.