Skip to main content

Synthesis of modified fragments of fibrinogen and their effect on the activity of proteolytic enzymes


New analogues of the Gly-Pro-Arg and Arg-Gly-Asp fragments of fibrinogen were synthesized: Gly-Pro-Arg-Pro (I), Gly-Pro-Arg-Pro-Met-OMe (II), Gly-Pro-Arg-Pro-Phe (III), Gly-Pro-Arg-Pro-Asp (IV), Gly-Pro-Arg-Pro-Glu (V), and Arg-Asn-Trp-Asp (VI). Their effect on the activity of proteases of various types was studied with the method of lysis of fibrin plates. All the peptides were found to inhibit plasmin activity (by 60–85%) and the γ-subunit of nerve growth factor (by 55–93%). Tetrapeptide (VI) proved to be an effective inhibitor of tissue activator of plasminogen and the γ-subunit of nerve growth factor (by 96 and 93%, respectively). The peptides exerted practically no effect on the activity of urokinase and moderately inhibited the activity of streptokinase [(III), IV), and (VI)], papain [(I), (II), IV), and (VI)], subtilisin [(V) and (VI)], α-chymotrypsin [(III), (V), and VI)], and Bacillus subtilis metalloprotease (VI). They inhibit trypsin [except for (I) and (III)] when applied on fibrin plates at a concentration of 1 × 10−2 M, while, at the concentration of 1 × 10−3 M, (I) and (II) induced an increase in proteolytic activity by 35 and 47%, respectively.

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







nerve growth factor








tissue activator of plasminogen




  1. Laudano, A.P. and Doolitle, R.F., Proc. Natl. Acad. Sci. USA, 1978, vol. 75, pp. 3085–3089.

    PubMed  CAS  Google Scholar 

  2. Plow, E.F., Pierschbacher, M.D., Ruoslahti, E., Marguerie, G.A., and Ginsberg, M.H., Blood, 1987, vol. 70, pp. 110–115.

    PubMed  CAS  Google Scholar 

  3. Zablocki, A.F., Miyano, M., Rao, S.N., Panzer-Knodle, S., Nicholson, N., and Feigen, L., J. Med. Chem., 1992, vol. 35, pp. 4914–4917.

    Article  PubMed  CAS  Google Scholar 

  4. Cheng, S., Craig, W.S., Mullen, D., Tschopp, J.F., Dixon, D., and Pierschbacher, M.D., J. Med. Chem., 1994, vol. 37, pp. 1–8.

    PubMed  CAS  Google Scholar 

  5. Bogdanovich-Knipp, S.J., Chakrabarti, S., Williams, T.D., Dillman, R.K., and Siahaan, T.J., J. Peptide Res., 1999, vol. 53, pp. 530–541.

    Google Scholar 

  6. Song, X., Xu, C.R., He, H.T., and Siahaan, T.J., Bioorg. Chem., 2002, vol. 30, pp. 285–301.

    Article  PubMed  CAS  Google Scholar 

  7. Krys’ko, A.A., Malovichko, O.L., Kabanova, T.A., and Mazepa, A.V., Rus. J. Bioorg. Chem., 2004, vol. 30, pp. 534–538.

    CAS  Google Scholar 

  8. Levitskaya, N.G., Kleimenov, L.N., Petrosyan, M.T., Rozenfel’d, M.A., Kalikhevich, V.N., and Ardemasova, Z.A., Byull. Eksp. Biol. Med., 1988, vol. 104, pp. 190–192.

    Google Scholar 

  9. Laudano, A.P. and Doolitle, R.F., Biochemistry, 1980, vol. 19, pp. 1013–1019.

    Article  PubMed  CAS  Google Scholar 

  10. Kawasaki, K., Tsuji, T., and Hirase, K., Chem. Pharm. Bull., 1991, vol. 39, pp. 584–589.

    PubMed  CAS  Google Scholar 

  11. Yanchenko, V.V., Martinovich, V.P., Mel’nik, O.V., Golubovich, V.P., Novikov, P.D., Novikov, D.K., and Shrestkha, K.G., Immunopatol., Allergol., Infektol., 2004, no. 3, pp. 22–32.

  12. Nikandrov, V.N., Pyzhova, N.S., and Votyakov, V.I., Vopr. Med. Khim., 1987, vol. 33, pp. 84–87.

    PubMed  CAS  Google Scholar 

  13. Madison, E.L., Coombs, G.S., and Corey, D.R., J. Biol. Chem., 1995, vol. 270, pp. 7558–7562.

    PubMed  CAS  Google Scholar 

  14. Nikandrov, V.N., Novosti Mediko-biol. Nauk, 2004, no. 3, pp. 127–146.

  15. Andreenko, G.V. and Migalinya, L.A., Biokhimiya (Moscow), 1974, vol. 36, pp. 685–689.

    Google Scholar 

  16. Brockway, W.J. and Castellino, F., J. Biol. Chem., 1971, vol. 246, pp. 4641–4647.

    CAS  Google Scholar 

  17. Buravskii, V.A., Gorbunova, N.B., Koltunov, V.V., Lukashevich, V.S., and Polukoshko, E.F., Izv. Akad. Nauk BSSR, Ser. Biol., 1984, no. 4, pp. 79–84.

  18. Lukashevich, V.S., Izv. Akad. Nauk BSSR, Ser. Biol., 1987, no. 3, pp. 80–82.

  19. Pyzhova, N.S., Nikandrov, V.N., and Nikandrov, N.N., Thromb. Res., 1996, vol. 82, pp. 303–312.

    Article  PubMed  CAS  Google Scholar 

  20. Nikandrov, V.N. and Pyzhova, N.S., USSR Inventor’s Certificate no. 1 472 508, 1988.

  21. Wohl, R.C., Arzadon, L., Summania, L., and Robbins, K., J. Biol. Chem., 1977, vol. 252, pp. 1141–1147.

    PubMed  CAS  Google Scholar 

  22. Kirschenbaum, D.M., Anal. Biochem., 1975, vol. 68, pp. 465–484.

    Article  PubMed  CAS  Google Scholar 

  23. Cederholm-Williams, S.A. and Swain, A., Thromb. Res., 1979, vol. 16, pp. 705–713.

    Article  PubMed  CAS  Google Scholar 

  24. Mosolov, V.V., Proteoliticheskie fermenty (Proteolytic Enzymes), Moscow: Nauka, 1971.

    Google Scholar 

  25. Slugterman, L.A. and Wijdenes, J., Biochem. Biophys. Acta, 1970, vol. 200, pp. 593–595.

    Google Scholar 

  26. Gorodetskii, D.I., Myasoedov, N.F., and Stepanov, V.M., Biokhimiya (Moscow), 1975, vol. 40, pp. 1305–1311.

    CAS  Google Scholar 

  27. Bradford, M.M., Anal. Biochem., 1976, vol. 72, pp. 248–254.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to V. P. Martinovich.

Additional information

Original Russian Text © V.N. Nikandrov, N.S. Pyzhova, V.P. Golubovich, O.V. Mel’nik, V.P. Martinovich, 2006, published in Bioorganicheskaya Khimiya, 2006, Vol. 32, No. 2, pp. 144–150.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Nikandrov, V.N., Pyzhova, N.S., Golubovich, V.P. et al. Synthesis of modified fragments of fibrinogen and their effect on the activity of proteolytic enzymes. Russ J Bioorg Chem 32, 129–135 (2006).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

Key words

  • fragments of fibrinogen
  • synthesis of analogues
  • effect on activity of proteases