Small synthetic inhibitors of cysteine proteases

Summary

This article focuses on the development of small synthetic inhibitors of cysteine proteases since 1990. The emphasis is on the design of selective cysteine protease inhibitors as research tools and as potential therapeutic agents. The mechanisms of inhibition of the new compounds, where appropriate, are discussed, and also how a knowledge of the differences in mechanisms between cysteine and serine proteases may be exploited in the design of selective inhibitors.

This is a preview of subscription content, access via your institution.

References

  1. 1

    Shaw, E., Adv. Enzymol. Relat. Areas Mol. Biol., 63 (1990) 271.

    Google Scholar 

  2. 2

    Demuth, H.-U., J. Enzyme Inhib., 3 (1990) 249.

    Google Scholar 

  3. 3

    Shaw, E., Methods Enzymol., 244 (1994) 649.

    Google Scholar 

  4. 4

    Krantz, A., Methods Enzymol., 244 (1994) 656.

    Google Scholar 

  5. 5

    Brömme, D. and Demuth, H.-U., Methods Enzymol., 244 (1994) 671.

    Google Scholar 

  6. 6

    Barrett, A.J. and Salvesen, G. (Eds.) Proteinase Inhibitors, Research Monographs in Cell and Tissue Physiology, Vol. 12, Elsevier, New York, NY, U.S.A., 1986.

    Google Scholar 

  7. 7

    Mizuochi, T., Yee, S.T., Kasai, M., Kakiuchi, T., Muno, D. and Kominami, E., Immunol. Lett., 43 (1994) 189.

    Google Scholar 

  8. 8

    Tezapsidis, N., Noctor, S., Kannan, R., Krieger, T.J., Mende-Mueller, L. and Hook, V.Y., J. Biol. Chem., 270 (1995) 13285.

    Google Scholar 

  9. 9

    Hook, V.Y., Azaryan, A.V., Hwang, S.R. and Tezapsidis, N., FASEB J., 8 (1994) 1269.

    Google Scholar 

  10. 10

    Silberring, J., Demuth, H.-U., Brostedt, P. and Nyberg, F., J. Biochem., 114 (1993) 648.

    Google Scholar 

  11. 11

    Sherwood, S.W., Kung, A.L., Roitelman, J., Simoni, R.D. and Schimke, R.T., Proc. Natl. Acad. Sci. USA, 90 (1993) 3353.

    Google Scholar 

  12. 12

    Patel, Y., Wheeler-Jones, C.P., Sadowska, K., Kakkar, V.V. and Krishnamurthi, S., Br. J. Pharmacol., 98 (Suppl.) (1989) 846P.

    Google Scholar 

  13. 13

    Van Noorden, C.J. and Everts, V., Biochem. Biophys. Res. Commun., 178 (1991) 178.

    Google Scholar 

  14. 14

    Mashima, T., Naito, M., Kataoka, S., Kawai, H. and Tsuruo, T., Biochem. Biophys. Res. Commun., 209 (1995) 907.

    Google Scholar 

  15. 15

    Tewari, M. and Dixit, V.M., J. Biol. Chem., 270 (1995) 3255.

    Google Scholar 

  16. 16

    Thornberry, N.A., Peterson, E.P., Zhao, J.J., Howard, A.D., Griffin, P.R. and Chapman, K.T., Biochemistry, 33 (1994) 3934.

    Google Scholar 

  17. 17

    Kamens, J., Paskind, M., Hugunin, M., Talanian, R.V., Allen, H., Banach, D., Bump, N., Hackett, M., Johnston, C.G., Li, P., Mankovich, J.A., Terranova, M. and Ghayur, T., J. Biol. Chem., 270 (1995) 15250.

    Google Scholar 

  18. 18

    Edelstein, C.L., Wieder, E.D., Yaqoob, M.M., Gengaro, P.E., Burke, T.J., Memenoff, R.A. and Schrier, R.W., Proc. Natl. Acad. Sci. USA, 92 (1995) 7662.

    Google Scholar 

  19. 19

    Baricos, W.H., O'Connor, S.E., Cortez, S.L., Wu, L.T. and Shah, S.V., Biochem. Biophys. Res. Commun., 155 (1988) 1318.

    Google Scholar 

  20. 20

    Baricos, W.H., Cortez, S.L., Le, Q.C., Wu, L.T., Shaw, E., Hanada, K. and Shah, S.V., Arch. Biochem. Biophys., 288 (1991) 468.

    Google Scholar 

  21. 21

    Thorne, D.P. and Lockwood, T.D., Am. J. Physiol., 265 (1993) 10.

    Google Scholar 

  22. 22

    Lizuka, K., Kawaguchi, H. and Kitabatake, A., J. Mol. Cell. Cardiol., 25 (1993) 1101.

    Google Scholar 

  23. 23

    Atsma, D.E., Bastiaanse, E.M., Jerzewski, A., Van der Valk, L.J. and Van der Laarse, A., Circ. Res., 76 (1995) 1071.

    Google Scholar 

  24. 24

    Iizuka, K., Kawaguchi, H. and Kitabatake, A., J. Mol. Cell. Cardiol., 25 (1993) 1101.

    Google Scholar 

  25. 25

    Warner, A.H. and Ryan, M.A., J. Mol. Cell. Cardiol., 22 (1990) 577.

    Google Scholar 

  26. 26

    Tsuchida, K., Aihara, H., Isogai, K., Hanada, K. and Shibata, N., Biol. Chem. Hoppe-Seyler, 367 (1986) 39.

    Google Scholar 

  27. 27

    Inoue, S., Sharma, R.C., Schimke, R.T. and Simoni, R.D., J. Biol. Chem., 268 (1993) 5894.

    Google Scholar 

  28. 28

    Mellgren, R.L., Shaw, E. and Mericle, M.T., Exp. Cell Res., 215 (1994) 164.

    Google Scholar 

  29. 29

    Crawford, C., Mason, R.W., Wikstrom, P. and Shaw, E., Biochem. J., 253 (1988) 751.

    Google Scholar 

  30. 30

    Ermer, A., Baumann, H., Steude, G., Peters, K. Fittkau, S., Dolaschka, P. and Genov, N.C., J. Enzyme Inhib., 4 (1990) 35.

    Google Scholar 

  31. 31

    Rasnick, D., Anal. Biochem., 149 (1985) 461.

    Google Scholar 

  32. 32

    Shaw, E., Angliker, H., Rauber, P., Walker, B. and Wikstrom, P., Biomed. Biochim. Acta, 45 (1986) 1397.

    Google Scholar 

  33. 33

    Angliker, H., Anagli, J. and Shaw, E., J. Med. Chem., 35 (1992) 216.

    Google Scholar 

  34. 34

    Anagli, J., Hagmann, J. and Shaw, E., Biochem. J., 289 (1993) 93.

    Google Scholar 

  35. 35

    Angliker, H., Wikstrom, P., Rauber, P. and Shaw, E., Biochem. J., 241 (1987) 871.

    Google Scholar 

  36. 36

    Huang, Z., McGowan, E.B. and Detwiler, T.C., J. Med. Chem., 35 (1992) 2048.

    Google Scholar 

  37. 37

    Wagner, B.M., Smith, R.A., Coles, L.J., Ernest, M.J. and Krantz, A., J. Med. Chem., 37 (1994) 1833.

    Google Scholar 

  38. 38

    Tachikura, T., Acta Paediatr. Jpn. Overs. Ed., 32 (1990) 495.

    Google Scholar 

  39. 39

    Etherington, D.J., Taylor, M.A.J. and Henderson, B., Br. J. Exp. Pathol., 69 (1988) 281.

    Google Scholar 

  40. 40

    Buttle, D.J., Saklatvala, J., Tamai, M. and Barrett, A.J., Biochem. J., 281 (1992) 175.

    Google Scholar 

  41. 41

    Maciewicz, R.A. and Etherington, D.J., Biochem. Soc. Trans., 16 (1988) 812.

    Google Scholar 

  42. 42

    Mort, J.S. and Recklies, A.D., Arthritis Rheum., 27 (1984) 509.

    Google Scholar 

  43. 43

    Trabandt, A., Gay, R.E., Fassbender, H.-G. and Gay, S., Arthritis Rheum., 34 (1991) 1444.

    Google Scholar 

  44. 44

    Van Noorden, C.J., Smith, R.E. and Rasnick, D., J. Rheumatol., 15 (1988) 1525.

    Google Scholar 

  45. 45

    Esser, R.E., Watts, L.M., Angelo, R.A., Thornburg, L.P., Prior, J.J. and Palmer, J.T., J. Rheumatol., 20 (1993) 1176.

    Google Scholar 

  46. 46

    Esser, R.E., Angelo, R.A., Murphey, M.D., Watts, L.M., Thornburg, L.P., Palmer, J.T., Talhouk, J.W. and Smith, R.E., Arthritis Rheum., 37 (1994) 236.

    Google Scholar 

  47. 47

    Ahmed, N.K., Martin, L.A., Watts, L.M., Palmer, J., Thornburg, L., Prior, J. and Esser, R.E., Biochem. Pharmacol., 44 (1993) 1201.

    Google Scholar 

  48. 48

    Sheahan, K., Shuja, S. and Murnane, M.J., Cancer Res., 49 (1989) 3809.

    Google Scholar 

  49. 49

    Yagel, S., Warner, A.H., Nellans, H.N., Lala, P.K., Waghorne, C. and Denhardt, D.T., Cancer Res., 49 (1989) 3553.

    Google Scholar 

  50. 50

    Lah, T.T., Buck, M.R., Honn, K.V., Crissman, J.D., Rao, N.C., Liotta, L.A. and Sloane, B.F., Clin. Exp. Metastasis, 7 (1989) 461.

    Google Scholar 

  51. 51

    Alidina, R., Kikuchi, M., Kashima, M., Epstein, J.H. and Fukuyama, K., Exp. Mol. Pathol., 49 (1988) 118.

    Google Scholar 

  52. 52

    Persky, B., Ostrowski, L.E., Pagast, P., Ahsan, A. and Schultz, R.M., Cancer Res., 46 (1986) 4129.

    Google Scholar 

  53. 53

    Azuma, M., David, L.L. and Shearer, T.R., Curr. Eye Res., 10 (1991) 657.

    Google Scholar 

  54. 54

    Shearer, T.R., Azuma, M., David, L.L. and Murachi, T., Invest. Ophthalmol. Vis. Sci., 32 (1991) 533.

    Google Scholar 

  55. 55

    McGrath, M.E., Eakin, A.E., Engel, J.C., McKerrow, J.H., Craik, C.S. and Fletterick, R.J., J. Mol. Biol., 247 (1995) 251.

    Google Scholar 

  56. 56

    Ring, C.S., Sun, E., McKerrow, J.H., Lee, G.K., Rosenthal, P.J., Kuntz, I.D. and Cohen, F.E., Proc. Natl. Acad. Sci. USA, 90 (1993) 3583.

    Google Scholar 

  57. 57

    Rosenthal, P.J., McKerrow, J.H., Rasnick, D. and Leech, J.H., Mol. Biochem. Parasitol., 35 (1989) 177.

    Google Scholar 

  58. 58

    Rosenthal, P.J., Wollish, W.S., Palmer, J.T. and Rasnick, D., J. Clin. Invest., 88 (1991) 1467.

    Google Scholar 

  59. 59

    Bode, W., Engh, R., Musil, D., Laber, B., Stubbs, M., Huber, R. and Turk, V., Biol. Chem. Hoppe-Seyler, 371 (1990) 111.

    Google Scholar 

  60. 60

    Gorbalenya, A.E., Donchenko, A.P., Blinov, V.M. and Koonin, E.V., FEBS Lett., 243 (1989) 103.

    Google Scholar 

  61. 61

    Bazan, J.F. and Fletterick, R.J., Proc. Natl. Acad. Sci. USA, 85 (1988) 7872.

    Google Scholar 

  62. 62

    Cho, K., Anal. Biochem., 164 (1987) 248.

    Google Scholar 

  63. 63

    Brocklehurst, K.B., Willenbrook, F.S. and Salih, E., In Neuberger, A. and Brocklehurst, K.B. (Eds.) Hydrolytic Enzymes, New Comprehensive Biochemistry, Vol. 16, Elsevier, Amsterdam, The Netherlands, 1987, p. 39.

    Google Scholar 

  64. 64

    Campbell, P., Nashed, N.Y., Lapinskas, B.A. and Gurrieri, J., J. Biol. Chem., 258 (1983) 59.

    Google Scholar 

  65. 65

    Asboth, B. and Polgar, L., Biochemistry, 22 (1983) 117.

    Google Scholar 

  66. 66

    Pliura, D.H., Bonaventura, B.J., Smith, R.A., Coles, P.J. and Krantz, A., Biochem. J., 288 (1992) 759.

    Google Scholar 

  67. 67

    Smith, R.A., Copp, L.J., Donnelly, S.L., Spencer, R.W. and Krantz, A., Biochemistry, 27 (1988) 6568.

    Google Scholar 

  68. 68

    Krantz, A., Copp, L.J., Coles, P.J., Smith, R.A. and Heard, S.B., Biochemistry, 30 (1991) 4678.

    Google Scholar 

  69. 69

    Brömme, D., Smith, R.A., Coles, P.J., Kirschke, H., Storer, A.C. and Krantz, A., Biol. Chem. Hoppe-Seyler, 375 (1994) 343.

    Google Scholar 

  70. 70

    Dolle, R.E., Singh, J., Rinker, J., Hoyer, D., Prasad, C.V., Graybill, T.L., Salvino, J.M., Helaszek, C.T., Miller, R.E. and Ator, M.A., J. Med. Chem., 37 (1994) 3863.

    Google Scholar 

  71. 71

    Shaw, E., J. Biol. Chem., 263 (1988) 2768.

    Google Scholar 

  72. 72

    Pliura, D.H., Bonaventura, B.J., Paulis, H.W., Killackey, J.F. and Krantz, A., J. Enzyme Inhib., 6 (1992) 181.

    Google Scholar 

  73. 73

    Li, Z., Patil, G.S., Golubski, Z.E., Hori, H., Tehrani, K., Foreman, J.E., Eveleth, D.D., Bartus, R.T. and Powers, J.C., J. Med. Chem., 36 (1993) 3472.

    Google Scholar 

  74. 74

    Hanzlik, R.P. and Thompson, S.A., J. Med. Chem., 27 (1984) 711.

    Google Scholar 

  75. 75

    Palmer, J.T., Rasnick, D., Klaus, J.L. and Brömme, D., J. Med. Chem., 38 (1995) 3193.

    Google Scholar 

  76. 76

    Thompson, S.A., Andrews, P.R. and Hanzlik, R.P., J. Med. Chem., 29 (1986) 104.

    Google Scholar 

  77. 77

    Magrath, J. and Abeles, R.H., J. Med. Chem., 35 (1992) 4279.

    Google Scholar 

  78. 78

    Martichonok, V., Plouffe, C., Storer, A.C., Ménard, R. and Jones, J.B., J. Med. Chem., 38 (1995) 3078.

    Google Scholar 

  79. 79

    Brömme, D., Neumann, U., Kirschke, H. and Demuth, H.-U., Biomed. Biochim. Acta, 1202 (1993) 271.

    Google Scholar 

  80. 80

    Brömme, D. and Kirschke, H., FEBS Lett., 322 (1993) 211.

    Google Scholar 

  81. 81

    Robinson, V.J., Coles, P.J., Smith, R.A. and Krantz, A., J. Am. Chem. Soc., 113 (1991) 7760.

    Google Scholar 

  82. 82

    Ménard, R., Feng, R., Storer, A.C., Robinson, V.J., Smith, R.A. and Krantz, A., FEBS Lett., 295 (1991) 27.

    Google Scholar 

  83. 83

    Fuchs, P.L. and Braish, T.F., Chem. Rev., 86 (1986) 903.

    Google Scholar 

  84. 84

    Simpkins, N.S., Tetrahedron, 46 (1990) 6951.

    Google Scholar 

  85. 85

    Liu, S. and Hanzlik, R.P., J. Med. Chem., 35 (1992) 1067.

    Google Scholar 

  86. 86

    Brocklehurst, K. and Malthouse, J.P.G., Biochem. J., 175 (1978) 761.

    Google Scholar 

  87. 87

    Asboth, B., Stokum, E., Khan, I.U. and Polgar, L., Biochemistry, 24 (1985) 606.

    Google Scholar 

  88. 88

    Duncan, G.D., Huber, C.P. and Welsch, W.J., J. Am. Chem. Soc., 114 (1992) 5784.

    Google Scholar 

  89. 89

    Arad, D., Langridge, R. and Kollman, P.A., J. Am. Chem. Soc., 112 (1990) 491.

    Google Scholar 

  90. 90

    Arad, D., Kreisberg, R. and Shokhen, M., J. Chem. Inf. Comput. Sci., 33 (1993) 345.

    Google Scholar 

  91. 91

    Johnson, F.A., Lewis, S.D. and Shafer, J.A., Biochemistry, 20 (1981) 44.

    Google Scholar 

  92. 92

    Frankfater, A. and Kuppy, T., Biochemistry, 20 (1981) 5517.

    Google Scholar 

  93. 93

    Hanzlik, R.P., Zygmunt, J. and Moon, J.B., Biochim. Biophys. Acta, 1035 (1990) 62.

    Google Scholar 

  94. 94

    Dufour, E., Storer, A.C. and Menard, R., Biochemistry, 34 (1995) 9136.

    Google Scholar 

  95. 95

    Brömme, D., Bartels, B., Kirschke, H. and Fittkau, S., J. Enzyme Inhib., 3 (1989) 13.

    Google Scholar 

  96. 96

    Peters, K. and Fittkau, S., Biomed. Biochim. Acta, 49 (1990) 173.

    Google Scholar 

  97. 97

    Walker, B., McCarthy, N., Healy, A., Ye, T. and Mckervey, M.A., Biochem. J., 293 (1993) 321.

    Google Scholar 

  98. 98

    Angelastro, M.R., Mehdi, S., Burkhart, J.P., Peet, N.P. and Bey, P., J. Med. Chem., 33 (1990) 11.

    Google Scholar 

  99. 99

    Harbeson, S.L., Abelleira, S.M., Akiyama, A., Barrett, R., Carroll, R.M., Straub, J.A., Tkacz, J.N., Wu, C. and Musso, G.F., J. Med. Chem., 37 (1994) 2918.

    Google Scholar 

  100. 100

    Hu, L.Y. and Abeles, R.H., Arch. Biochem. Biophys. 281 (1990) 271.

    Google Scholar 

  101. 101

    Bastos, M., Maeji, N.J. and Abeles, R.H., Proc. Natl. Acad. Sci. USA, 92 (1995) 6738.

    Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Rasnick, D. Small synthetic inhibitors of cysteine proteases. Perspectives in Drug Discovery and Design 6, 47–63 (1996). https://doi.org/10.1007/BF02174045

Download citation

Keywords

  • Polymer
  • Cysteine
  • Serine
  • Protease Inhibitor
  • Therapeutic Agent