Skip to main content
SpringerLink
Log in

Elucidation of a common structure of selective fibrinogen receptor antagonists

  • Published:
Journal of Computer-Aided Molecular Design Aims and scope Submit manuscript

Abstract

In this paper, we investigate the common structural and electrostatic parameters of a series of specific inhibitors of the αIIbβ3 integrin. Molecular dynamics simulations with an explicit aqueous environment led to an original theoretical pattern. Our results may suggest that the studied non-peptide αIIbβ3 antagonists developed upon the Arg-Gly-Asp ubiquitous recognition sequence, in fact, should mimic the C-terminus part of the fibrinogen γ chain. This assumption could, therefore, explain their specificity with respect to other Arg-Gly-Asp-dependent integrins.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Phillips, D.R., Charo, I.F., Parsie, L.V. and Fitzgerald, L.A., Blood, 71 (1988) 831.

    Google Scholar 

  2. Marguerie, G.A., Plow, E.F. and Edington, T.S., J. Biol. Chem., 254 (1979) 5357.

    Google Scholar 

  3. Coller, B.S., N. Engl. J. Med., 322 (1990) 33.

    Google Scholar 

  4. Jakubowski, J.A., Smith, G.F. and Sall, D.J., Annu. Rep. Med. Chem., 27 (1992) 99.

    Google Scholar 

  5. Plow, E.F., Piersbacher, M.D., Ruoslahti, E., Marguerie, G.A. and Ginsberg, M.H., Proc. Natl. Acad. Sci. USA, 82 (1985) 8057.

    Google Scholar 

  6. Gartner, T.K. and Bennet, J.S., J. Biol. Chem., 260 (1985) 11891.

    Google Scholar 

  7. Hawiger, J., Kloczewiak, M., Bedmarek, M.A. and Timmons, S., Biochemistry, 28 (1989) 2909.

    Google Scholar 

  8. Plow, E.F., D'souza, S.E. and Ginsberg, M.H., Sem. Thromb. Haemostas., 18 (1992) 324.

    Google Scholar 

  9. Kloczewiak, M., Timmons, S., Lukas, T.J. and Hawiger, J., Biochemistry, 23 (1984) 1767.

    Google Scholar 

  10. Timmons, S., Kloczewiak, M. and Hawiger, J., Proc. Natl. Acad. Sci. USA, 81 (1984) 4935.

    Google Scholar 

  11. Plow, E.F., Srouji, A.H., Meyer, D., Marguerie, G. and Ginsberg, M.H., J. Biol. Chem., 259 (1984) 5388.

    Google Scholar 

  12. D'souza, S.E., Ginsberg, M.H., Burke, T.A. and Plow, E.F., J. Biol. Chem., 265 (1990) 3440.

    Google Scholar 

  13. Weller, T., Alig, L., Müller, M.H., Kouns, W.C. and Steiner, B., Drugs Future, 19 (1994) 461.

    Google Scholar 

  14. Gehlsen, K.R., Davis, G.E. and Sriramarao, P., Clin. Exp. Metastasis, 10 (1992) 111.

    Google Scholar 

  15. Hart, I.R., Birch, M. and Marshall, J.F., Cancer Metastasis Rev., 10 (1991) 115.

    Google Scholar 

  16. Davies, J., Warwick, J., Totty, N., Philp, R., Helfrich, M. and Horton, M., J. Cell. Biol., 109 (1989) 1817.

    Google Scholar 

  17. Lakkakorpi, P.T., Horton, M.A., Helfrich, M., Karhukorpi, E.K. and Vaanonen, H.K., J. Cell. Biol., 115 (1991) 1179.

    Google Scholar 

  18. Nikiforovich, G.V., Int. J. Pept. Protein Res., 44 (1994) 513.

    Google Scholar 

  19. Kirkpatrick, S., Gelatt, C.D. and Vechi, M.P., Science, 220 (1983) 671.

    Google Scholar 

  20. Verlet, L., Phys. Rev., 159 (1967) 98.

    Google Scholar 

  21. Berendsen, H.J.C., Postma, J.P.M., van Gunsteren, W.F., DiNola, A. and Haak, J.R., J. Chem. Phys., 81 (1984) 3684.

    Google Scholar 

  22. Cotrait, M., Kreissler, M., Hoflack, J., Lehn, J.-M. and Maigret, B., J. Comput.-Aided. Mol. Design, 6 (1992) 113.

    Google Scholar 

  23. Greenspoon, N., Hershkoviz, R., Alon, R., Varon, D., Shenkman, B., Marx, G., Federman, S., Kapustina, G. and Lider, O., Biochemistry, 32 (1993) 10001.

    Google Scholar 

  24. Gould, R.J., Chang, C., Lynch, R.J., Manno, P.D., Zhang, G., Bednar, B., Friedman, P.A., Egbertson, M., Turchi, L.M., Anderson, P.S. and Hartman, G., Thrombos. Haemostas., 69 (1993) 976.

    Google Scholar 

  25. Hartman, G.D., Egbertson, M.S., Halczenko, W., Laswell, W.L., Duggan, M.E., Smith, R.L., Naylor, A.M., Manno, P.D., Lynch, R.J., Zhang, G., Chang, C.T.-C. and Gould, R.J., J. Med. Chem., 35 (1992) 4640.

    Google Scholar 

  26. Alig, L., Edenforder, A., Hadváry, P., Hürzeler, M., Knopp, D., Müller, M., Steiner, B., Trzeciak, A. and Weller, T.J., J. Med. Chem., 35 (1992) 4393.

    Google Scholar 

  27. Cox, D., Aoki, T., Seki, J. and Motoyama, Y., Thrombos. Haemostas., 69 (1993) 706.

    Google Scholar 

  28. Fauchère, J.-L., Morris, A.D., Thurieau, C., Simonet, S., Verbeuren, T. and Kieffer, N., Int. J. Pept. Protein Res., 42 (1993) 440.

    Google Scholar 

  29. Scarborough, R.M., Rose, J.W., Naughton, M.A., Phillips, D.R., Nannizzi, L., Arfsten, A., Campbell, A.M. and Charo, I.F., J. Biol. Chem., 268 (1993) 1058.

    Google Scholar 

  30. Scarborough, R.M., Naughton, M.A., Teng, W., Rose, J.W., Phillips, D.R., Nannizzi, L., Arfsten, A., Campbell, A.M. and Charo, I.F., J. Biol. Chem., 268 (1993) 1066.

    Google Scholar 

  31. D'souza, S.E., Ginsberg, M.H., Matsueda, G.R. and Plow, E.F., Nature, 350 (1991) 66.

    Google Scholar 

  32. Mulliken, R.S., J. Chem. Phys., 23 (1955) 1833, 1848, 2338, 2343.

    Google Scholar 

  33. Donahue, J.P., Patel, H., Anderson, W.F. and Hawiger, J., Proc. Natl. Acad. Sci. USA, 91 (1994) 12178.

    Google Scholar 

  34. Mayo, K.H., Burke, C., Lindon, J.N. and Kloczewiak, M., Biochemistry, 29 (1990) 3277.

    Google Scholar 

  35. Scarborough, R.M., Rose, J.W., Hsu, M.A., Phillips, D.A., Fried, V.A., Campbell, A.M., Nannizzi, L. and Charo, I.F., J. Biol. Chem., 226 (1991) 9359.

    Google Scholar 

  36. Gulino, D., Boudignon, C., Zhang, L., Concord, E., Rabiet, M.-J. and Marguerie, G., J. Biol. Chem., 267 (1992) 1001.

    Google Scholar 

  37. Phillips, D.R., Charo, I.F. and Scarborough, R.M., Cell, 65 (1991) 359.

    Google Scholar 

  38. McDowell, R.S. and Gadek, T.R., J. Am. Chem. Soc., 114 (1992) 9245.

    Google Scholar 

  39. Pfaff, M., Tangemann, K., Müller, B., Gurrath, M., Müller, G., Kessler, H., Timpl, R. and Engel, J., J. Biol. Chem., 269 (1994) 20233.

    Google Scholar 

  40. McDowell, R.S., Blackburn, B.K., Gadek, T.R., McGee, L.R., Rawson, T., Reynolds, M.E., Robarge, K.D., Somers, T.C., Thorsett, E.D., Tischler, M., Webb II, R.R. and Michael, C.V., J. Am. Chem. Soc., 116 (1994) 5077.

    Google Scholar 

  41. McDowell, R.S., Gadek, T.R., Barker, P.L., Burdick, D.J., Chan, K.S., Quan, C.L., Skelton, N., Struble, M., Thorsett, E.D., Tischler, M., Tom, J.Y.K., Webb, T.R. and Burnier, J.P., J. Am. Chem. Soc., 116 (1994) 5069.

    Google Scholar 

  42. D'souza, S.E., Ginsberg, M.H., Burke, T.A., Lam, S.C.-T. and Plow, E.F., Science, 242 (1988) 91.

    Google Scholar 

  43. Muller, T.H., Weisenberger, H., Brickl, R., Narjes, H., Himmelsbach, F. and Krause, J., Circulation, 96 (1997) 1130.

    Google Scholar 

  44. Eldred, C.D., Evans, B., Hindley, S., Judkins, B.D., Kelly, H.A., Kitchin, J., Lumley, P., Porter, B., Ross, B.C. and Smith, K.J., J. Med. Chem., 37 (1994) 3882.

    Google Scholar 

  45. Mayo, K.H., Fan, F., Beavers, M.P., Eckardt, A., Keane, P., Hoekstra, W.J. and Andrade-Gordon, P., Biochemistry, 35 (1996) 4434.

    Google Scholar 

  46. Gurrath, M., Müller, B., Kessler, H., Aumailley, M. and Timpl, R., Eur. J. Biochem., 210 (1992) 911.

    Google Scholar 

  47. Seetharam, D.S.J., Usman, S.F.T., Soma, C. and Teruna, J.S., J. Biomol. Struct. Dyn., 14 (1996) 1.

    Google Scholar 

  48. Hobohm, U. and Sander, C., Protein Sci., 3 (1994) 522.

    Google Scholar 

  49. Lam, S.C.-T., Plow, E.F., Smith, M.A., Andrieux, A., Ryckwaert, J.J., Marguerie, G. and Ginsberg, M.H., J. Biol. Chem., 262 (1987) 947.

    Google Scholar 

  50. Moitessier, N., Minoux, H., Maigret, B., Chrétien, F. and Chapleur, Y., Lett. Pept. Sci., 5 (1998) 75.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Groupe Biochimie Théorique, France

    Hervé Minoux, Nicolas Moitessier, Yves Chapleur & Bernard Maigret

  2. Groupe SUCRES, U.M.R. CNRS 7565, Université Henri Poincaré, Nancy I, BP 239, F-54506, Vandoeuvre-lès-Nancy Cedex, France

    Hervé Minoux, Nicolas Moitessier, Yves Chapleur & Bernard Maigret

Authors
  1. Hervé Minoux
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nicolas Moitessier
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yves Chapleur
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bernard Maigret
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Minoux, H., Moitessier, N., Chapleur, Y. et al. Elucidation of a common structure of selective fibrinogen receptor antagonists. J Comput Aided Mol Des 12, 533–542 (1998). https://doi.org/10.1023/A:1008024924329

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1008024924329

Search

Navigation