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Synthesis and properties of a new conformational antigen which models an extracellular region of β1-adrenoreceptor

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Abstract

Two fragments corresponding to the 125–133 and 206–218 sequences of a molecule of the β1-adrenoreceptor (autoantibodies to this protein are often found in patients with dilated cardiomyopathy) were synthesized by the solid phase method with the use of Fmoc technology. Two new conformational antigens were prepared by directed (regioselective) and undirected (spontaneous) formation of intramolecular and intermolecular disulfide bridges between the corresponding cysteine residues of the synthesized peptides. One of these antigens consisted of a mixture of disulfide isomers, and another antigen was an isomer with a natural arrangement of S-S bridges. Immunosorbents were obtained by immobilization of the synthesizes antigens on the bromocyanogen-activated sepharose and applied to the removal of autoantibodies in a β1-adrenoreceptor from the blood plasma of patients. We demonstrated that the sorbents on the basis of the conformational antigens were more effective in comparison with those containing linear peptide precursors.

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Abbreviations

Acm:

acetamidomethyl

DCMP:

dilated cardiomyopathy

DIC:

N,N′-diisopropylcarbodiimide

Fmoc:

9-fluorenylmethyloxycarbonyl

HOBt:

1-hydroxybenzotrazole

NMP:

N-methylpyrrolidone

TIBS:

triisobutylsilane

Pmc:

2,2,5,7,8-pentamethylchromane-6-sulfonyl

SPyr:

2-pyridinesulfenyl

SPPS:

solid phase peptide synthesis.

References

  1. San Martín, M.A., García, Á., Rodríguez, F.J., and Terol, I., Rev. Esp. Cardiol., 2002, vol. 55, no. 5, pp. 514–524.

    PubMed  Google Scholar 

  2. Fu, M. and Matsui, S., 2002, vol. 51, no. 4, pp. 208–212.

  3. Rönspeck, W., Brinckmann R,, Egner R., Gebauer F., Winkler D., Jekow P., Wallukat G., Müller J., Kunze R, Ther. Apher. Dial., 2003, vol. 7, no. 1, pp. 91–97.

    Article  PubMed  Google Scholar 

  4. Staudt, A., Schaper, F., Stangl, V., Plagemann, A., Bohm, M., Merkel, K., Wallukat, G., Wernecke, K.D., Stangl, K., Baumann, G., and Felix, S.B., Circulation, 2001, vol. 103, no. 22, pp. 2681–2686.

    PubMed  CAS  Google Scholar 

  5. Konovalov, G.A., Belenkov, Yu.N., Zvezdkin, P.V., Chebyshev, A.N., Semin, S.N., Kuznetsova, Yu.V., Adamova, I.Yu., Kipor, S.G., and Pokrovskii, S.N., Kardiologiya, 2002, no. 6, pp. 123–127.

  6. Matoba, Y., Okubo, H., and Nosé, Y., Artificial Organs, 2004, vol. 28, no. 2, pp. 171–181.

    Article  PubMed  Google Scholar 

  7. Magnusson, Y., Wallukat, G., Waagstein, F., Hjalmarson, A., and Hoebeke, J., Circulation, 1994, vol. 89, no. 6, pp. 2760–2767.

    PubMed  CAS  Google Scholar 

  8. Matsui, S., Fu, M.L., Hayase, M., Katsuda, S., Yamaguchi, N., Teraoka, K., Kurihara, T., and Takekoshi, N., J. Card. Fail., 1999, vol. 5, no. (3), pp. 246–254.

    Article  PubMed  CAS  Google Scholar 

  9. Zhang, L., Hu, D., Li, J., Wu, Y., Liu, X., and Yang, X., Chin. Med. J. (Engl.), 2002, vol. 115, no. 8, pp. 1127–1131.

    CAS  Google Scholar 

  10. Chiale, P.A., Ferrari, I., Mahler, E., Vallazza, M.A., and Elizari, M.V., Circulation, 2001, vol. 103, no. 13, pp. 1765–1771.

    PubMed  CAS  Google Scholar 

  11. Frielle, T., Collins, S., Daniel, K.W., Caron, M.G., Lefkowitz, R.J., and Kobilka, B.K., Proc. Natl. Acad. Sci. USA, 1987, vol. 84, pp. 7920–7924.

    Article  PubMed  CAS  Google Scholar 

  12. Tanea, K., Magnussonb, Y., Viguera, M., Lengagnea, R., Hjalmarsonb, A., Guilleta, J.B., and Hoebeeke, J., Biochimie, 1994, vol. 76, pp. 159–164.

    Article  Google Scholar 

  13. Iwata, M., Yoshikawa, T., Baba, A., Anzai, T., Nakamura, I., Wainai, Y., Takahashi, T., and Ogawa, S., Circulation Res., 2001, vol. 88, pp. 578–586.

    PubMed  CAS  Google Scholar 

  14. Shul’ts, G. and Shirmer, R., Printsipy strukturnoi organizatsii belkov (Principles of Structural Organization of Proteins), Moscow: Mir, 1982 [Russian translation].

    Google Scholar 

  15. Fraser, C.M., J. Biol. Chem., 1989, vol. 264, pp. 9266–9270.

    PubMed  CAS  Google Scholar 

  16. Andreu, D, Albericio, F, Sole, N.A, Munson, M.C, Ferrer, M, and Barany, G, in Peptide Synthesis Protocol, Pennington, M.W. and Dunn, B.M.., Eds., New Jersey, Totowa: Humana Press Inc, 1994, pp. 91–169.

    Chapter  Google Scholar 

  17. Kudryavtseva, E.V., Sidorova, M.V., Molokoedov, A.S., Ovchinnikov, M.V., and Bespalova, Zh.D., Bioorg. Khim., 1999, vol. 25, pp. 107–116.

    CAS  Google Scholar 

  18. Sidorova, M.V., Molokoedov, A.S., Az’muko, A.A., Kudryavtseva, E.V., Krause, E., Ovchinnikov, M.V., and Besralova, Zh.D., Bioorg. Khim., 2004, vol. 30, pp. 115–125 [Russ. J. Bioorg. Chem. (Engl. Transl.), vol. 30, pp. 101–110].

    PubMed  CAS  Google Scholar 

  19. Stewart, J.M. and Young, J.D., Solid Phase Peptide Synthesis, 2nd ed., Rockford, Il.: Pierse Chemical Co., 1984.

    Google Scholar 

  20. Khimiya Polipeptidov (Polypeptide Chemistry), Moscow: Mir, 1977 [Russian translation].

  21. Schmidt, M., Krause, E., Beyermann, M., and Bienert, M., Peptide Res., 1995, vol. 8, pp. 238–242.

    CAS  Google Scholar 

  22. Nguyen, D.N., Becker, G.W., and Riggin, R.M., J. Chromatography A, 1995, vol. 705, pp. 21–45.

    Article  CAS  Google Scholar 

  23. Porath, J., Biochimie, 1973, vol. 55, pp. 943–951.

    Article  CAS  Google Scholar 

  24. Bradford, M., Anal. Biochem., 1976, vol. 56, pp. 248–252.

    Article  Google Scholar 

Download references

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Authors and Affiliations

  1. Russian Cardiological Research and Production Complex, Russian Ministry of Public Health, ul. 3-ya Cherepkovskaya 15a, 121552, Moscow, Russia

    M. V. Sidorova, M. E. Pal’keeva, A. S. Molokoedov, A. A. Az’muko, A. V. Sekridova, M. V. Ovchinnikov, P. A. Levashov, O. I. Afanasieva, Yu. V. Berestetskaya, M. I. Afanasieva, O. A. Razova, Zh. D. Bespalova & S. N. Pokrovskii

Authors
  1. M. V. Sidorova
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  2. M. E. Pal’keeva
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  3. A. S. Molokoedov
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  4. A. A. Az’muko
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  5. A. V. Sekridova
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  6. M. V. Ovchinnikov
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  7. P. A. Levashov
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  8. O. I. Afanasieva
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  9. Yu. V. Berestetskaya
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  10. M. I. Afanasieva
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  11. O. A. Razova
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  12. Zh. D. Bespalova
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  13. S. N. Pokrovskii
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Corresponding author

Correspondence to M. V. Sidorova.

Additional information

Original Russian Text © M.V. Sidorova, M.E. Pal’keeva, A.S. Molokoedov, A.A. Az’muko, A.V. Sekridova, M.V. Ovchinnikov, P.A. Levashov, O.I. Afanasieva, Yu.V. Berestetskaya, M.I. Afanasieva, O.A. Razova, Zh.D. Bespalova, S.N. Pokrovskii, 2009, published in Bioorganicheskaya Khimiya, 2009, Vol. 35, No. 3, pp. 311–322.

Other abbreviations correspond to IUPAC-IUB: Eur. J. Biochem, 1994, vol. 183, pp. 9–37.

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Sidorova, M.V., Pal’keeva, M.E., Molokoedov, A.S. et al. Synthesis and properties of a new conformational antigen which models an extracellular region of β1-adrenoreceptor. Russ J Bioorg Chem 35, 285–295 (2009). https://doi.org/10.1134/S1068162009030029

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  • DOI: https://doi.org/10.1134/S1068162009030029

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