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A conformational analysis of biologically active RGD-containing cyclopentapeptides

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Abstract

The theoretical conformational analysis of the biologically active RGD-containing pentapeptide cyclo(-Arg-Gly-Asp-Phe-DVal-), an inhibitor of laminin P1 interaction with its receptor, was performed. The space of permissible torsional angles of the backbone of the molecule was studied by the Monte Carlo method. From the large number of predicted low-energy conformers with various packings of the cyclic moiety of this pentapeptide, only those were selected that corresponded to stable structures of the model linear tripeptide Ac-Ala-Gly-Asp-NHMe. This peptide simulated the spatial possibilities of the backbones of RGD-containing fragments of laminin, vitronectin, and fibronectin. We selected several dozen structures that may be potential biologically active conformers, but only a few of them were capable of forming stable intramolecular hydrogen bonds. We assumed that a biologically active conformer of cyclo(-Arg-Gly-Asp-Phe-DVal-) can be present in significant amounts in an equilibrium mixture in solution along with other conformers without necessarily dominating among them.

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References

  1. Hynes, R.O.,Cell (Cambridge, Mass.), 1992, vol. 59, pp. 11–25.

    Article  Google Scholar 

  2. Abraham, D.G., Nutt, E.M., Bednar, R.A., Bednar, B., Gould, R.J., and Duong, L.T.,Mol. Pharmacol., 1997, vol. 52, pp. 227–236.

    PubMed  CAS  Google Scholar 

  3. Mohri, H., Tanabe, J., Katoh, K., and Okubo, T.,Peptides, 1995, vol. 16, pp. 263–268.

    Article  PubMed  CAS  Google Scholar 

  4. Bowditch, R.D., Hariharan, M., Tominna, E.F., Smith, J.B., Yamada, K.M., Getzoff, E.D., and Ginsberg, M.H.,J. Biol. Chem., 1994, vol. 269, pp. 10856–10863.

    PubMed  CAS  Google Scholar 

  5. Yamada, K.M.,J. Biol. Chem., 1991, vol. 266, pp. 12809–12812.

    PubMed  CAS  Google Scholar 

  6. D’Souza, S.E., Ginsberg, M.H., and Plow, E.F.,Trends Biochem. Sci., 1991, vol. 16, pp. 246–250.

    Article  PubMed  CAS  Google Scholar 

  7. Muller, G., Gurrath, M., Kessler, H., and Timpl, R.,Angew. Chem., Int. Ed. Engl., 1992, vol. 31, pp. 326–328.

    Article  Google Scholar 

  8. Pfaff, M., Tangemann, K., Muller, B., Gurrath, M., Muller, G., Kessler, H., Timpl, R., and Engel, J.,J. Biol. Chem., 1994, vol. 269, pp. 20233–20238.

    PubMed  CAS  Google Scholar 

  9. Aumailley, M., Gurrath, M., Mueller, G., Calvete, J., Timpl, R., and Kessler, H.,FEBS Lett., 1991, vol. 291, pp. 50–54.

    Article  PubMed  CAS  Google Scholar 

  10. Gurrath, M., Mueller, G., Kessler, H., Aumailley, M., and Timpl, R.,Eur. J. Biochem., 1992, vol. 210, pp. 911–921.

    Article  PubMed  CAS  Google Scholar 

  11. Wermuth, J., Goodman, S.L., Jonczyk, A., and Kessler, H.,J. Am. Chem. Soc., 1997, vol. 119, pp. 1328–1335.

    Article  CAS  Google Scholar 

  12. Stradley, S.J., Rizo, J., Bruch, M.D., Stroup, A.M., and Gierasch, L.M.,Biopolymers, 1990, vol. 29, pp. 263–287.

    Article  PubMed  CAS  Google Scholar 

  13. Mierke, D.F., Kurz, M., and Kessler, H.,J. Am. Chem. Soc., 1994, vol. 116, pp. 1042–1049.

    Article  CAS  Google Scholar 

  14. Kopple, K.D., Bhandary, K.K., Kartha, G., Wang, Y., and Parameswaran, K.N.,J. Am. Chem. Soc., 1986, vol. 108, pp. 4637–4642.

    Article  CAS  Google Scholar 

  15. Kessler, H., Bats, J.W., Lautz, J., and Mueller, A.,Liebigs Ann. Chem., 1989, pp. 913–928.

  16. Kopple, K.D., Wang, Y., Cheng, A.G., and Bhandary, K.K.,J. Am. Chem. Soc., 1988, vol. 110, pp. 4168–4176.

    Article  CAS  Google Scholar 

  17. Kessler, H., Matter, H., Gemecker, G., Kottenhahn, M., and Bats, J.W.,J. Am. Chem. Soc., 1992, vol. 114, pp. 4805–4818.

    Article  CAS  Google Scholar 

  18. Perzel, A., Hollosi, M., Sandor, P., and Fasman, G.D.,Int. J. Peptide Protein Res., 1993, vol. 41, pp. 223–236.

    Article  Google Scholar 

  19. Sefler, A.M., Lauri, G., and Bartlett, P.A.,Int. J. Peptide Protein Res., 1996, vol. 48, pp. 129–138.

    Article  CAS  Google Scholar 

  20. Kostetsky, P.V. and Artem’ev, I.V.,Biokhimiya (Moscow), 1997, vol. 62, pp. 879–885.

    Google Scholar 

  21. Zimmerman, S.S., Pottle, M.S., Nemethy, G., and Scheraga, H.A.,Macromolecules, 1977, vol. 10, pp. 1–8.

    Article  PubMed  CAS  Google Scholar 

  22. Mammi, N.J., Hassan, M., and Goodman, M.,J. Am. Chem. Soc., 1985, vol. 107, pp. 4008–4013.

    Article  CAS  Google Scholar 

  23. Roos, H.M. and Van Rooyen, P.H.,Int. J. Peptide Protein Res., 1994, vol. 44, pp. 562–567.

    Article  CAS  Google Scholar 

  24. Kendrew, J.C., Klyne, W., Lifson, S., Miyazawa, T., Nemethy, G., Phillips, D.C., Ramachandran, G.N., and Scheraga, H.A.,Arch. Biochem. Biophys., 1971, vol. 145, pp. 405–421.

    Article  Google Scholar 

  25. Popov, E.M.,Strukturnaya organizatsiya belkov (Structural Organization of Proteins), Moscow: Nauka, 1992, pp. 60–81.

    Google Scholar 

  26. Reily, M.D., Thanabal, V., Omecinsky, D.O., Dunbar, J.B., Jr., Doherty, A.M., and DePue, P.L.,FEBS Lett., 1992, vol. 300, pp. 136–140.

    Article  PubMed  CAS  Google Scholar 

  27. Kessler, H., Klein, A.G., Obermeier, R., and Will, M.,Liebigs Ann. Chem., 1989, pp. 269–294.

  28. Nemethy, G. and Printz, M.P.,Macromolecules, 1972, vol. 5, pp. 755–758.

    Article  CAS  Google Scholar 

  29. Nemethy, G. and Scheraga, H.A.,Biochem. Biophys. Res. Commun., 1980, vol. 95, pp. 320–327.

    Article  PubMed  CAS  Google Scholar 

  30. Prachand, M.S., Dhingra, M.M., Saran, A., Coutinho, E., Bodi, J., Suli-Vargha, H., and Medzyhradszky, K.,J. Pept. Res, 1998, vol. 51, pp. 251–265.

    Article  PubMed  CAS  Google Scholar 

  31. Weiner, S.J., Kollman, P.A., Nguyen, D.T., and Case, D.A.,J. Comput. Chem., 1986, vol. 7, pp. 230–252.

    Article  CAS  Google Scholar 

  32. Howeler, U.,Moby: Molecular Modelling on the PC, Berlin: Springer, 1991.

    Google Scholar 

  33. Sobol’, T.M.,Metod Monte-Karlo (The Monte Carlo Method), Moscow: Nauka, 1968.

    Google Scholar 

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Authors and Affiliations

  1. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117871, GSP-7 Moscow, Russia

    P. V. Kostetsky & I. V. Artem’ev

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  1. P. V. Kostetsky
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  2. I. V. Artem’ev
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Correspondence to P. V. Kostetsky.

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Kostetsky, P.V., Artem’ev, I.V. A conformational analysis of biologically active RGD-containing cyclopentapeptides. Russ J Bioorg Chem 26, 262–270 (2000). https://doi.org/10.1007/BF02759165

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  • DOI: https://doi.org/10.1007/BF02759165

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