Skip to main content

The structure-antiaggregative activity relationship in a series of Arg-Gly-Asp analogues

Abstract

A series of analogues of Arg-Gly-Asp tripeptide, the common structural element of most of the integrin receptor ligands, possessing different conformational features for the interaction with platelet receptors, were synthesized by the methods of conventional peptide chemistry for use in the search for antithrombotic agents. The distance between the guanidine group of Arg and the β-carboxyl group of Asp was shown to affect the antiaggregative activity. A potent inhibitor of platelet aggregation, tripeptide Arg-βAla-Asp, with IC50 10.6 = 10.6 μM (ADP, 1.5 μM) was revealed.

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

Abbreviations

gAbu:

g-aminobutyric acid

bAla:

b-alanine

DAla:

D-alanine

FAB:

fast atom bombardment

HOBt:

N-hydroxybenzotriazole

TEA:

triethylamine

References

  1. Plow, E.F., Pierschbacher, M.D., Ruoslahti, E., Marguerie, G.A., and Ginsberg, M.H., Proc. Natl. Acad. Sci. USA, 1985, vol. 82, pp. 8057–8061.

    PubMed  CAS  Google Scholar 

  2. Pozdnyakova, T.M. and Belitser, N.V., Usp. Sovrem. Biol., 1990, vol. 110, pp. 267–283.

    CAS  Google Scholar 

  3. Plow, E.F., Marguerie, G.A., Pierschbacher, M.D., Ruoslahti, E., and Ginsberg, M.H., Proc. Natl. Acad. Sci. USA, 1982, vol. 79, pp. 3711–3715.

    PubMed  CAS  Google Scholar 

  4. Pierschbacher, M.D. and Ruoslahti, E., Proc. Natl. Acad. Sci. USA, 1984, vol. 81, pp. 5985–5989.

    PubMed  CAS  Google Scholar 

  5. Pueyo, C., Badimon, J.J., Royo, T., Feigen, L.P., and Badimon, L., Thromb. Res., 1996, vol. 81, pp. 101–112.

    Article  PubMed  CAS  Google Scholar 

  6. Zablocki, J.A., Miyano, M., Garland, R.B., Pireh, D., Schretzman, L.A., Rao, S.N., Lindmark, R.J., Panzer-Knodle, S.G., Nicholson, N.S., Taite, B.B., Salyers, A.K., King, L.W., Campion, J.G., and Feigen, L.P., J. Med. Chem., 1993, vol. 36, pp. 1811–1819.

    Article  PubMed  CAS  Google Scholar 

  7. Zablocki, J.A., Rico, J.G., Garland, R.B., Rogers, T.E., Williams, K., Schretzman, L.A., Rao, S.N., et al., J. Med. Chem., 1995, vol. 38, pp. 2378–2394.

    Article  PubMed  CAS  Google Scholar 

  8. Saudek, V., Atkinson, R.A., and Pelton, J.T., Biochemistry, 1991, vol. 30, pp. 7369–7372.

    PubMed  CAS  Google Scholar 

  9. Akhrem, A.A., Golubovich, V.P., Kirnarskii, L.I., and Galaktionov, S.G., Bioorg. Khim., 1976, vol. 4, pp. 838–840.

    Google Scholar 

  10. Akhrem, A.A., Golubovich, V.P., Galaktionov, S.G., Nikiforovich, G.V., Shenderovich, M.D., and Sherman, S.A., Izv. Akad. Nauk BSSR, Ser. Khim., 1976, no. 5, pp. 82–92.

  11. Born, G.V.R., Nature, 1962, vol. 194, pp. 927–929.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to O. V. Mel’nik.

Additional information

Original Russian Text © O.V. Mel’nik, V.P. Martinovich, V.P. Golubovich, 2006, published in Bioorganicheskaya Khimiya, 2006, Vol. 32, No. 2, pp. 137–143.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Mel’nik, O.V., Martinovich, V.P. & Golubovich, V.P. The structure-antiaggregative activity relationship in a series of Arg-Gly-Asp analogues. Russ J Bioorg Chem 32, 122–128 (2006). https://doi.org/10.1134/S1068162006020038

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1068162006020038

Key words

  • Arg-Gly-Asp peptide
  • peptide synthesis
  • platelet aggregation