Russian Journal of Bioorganic Chemistry

, Volume 33, Issue 2, pp 218–226 | Cite as

Peptide derivatives of tylosin-related macrolides

  • G. A. Korshunova
  • N. V. Sumbatyan
  • N. V. Fedorova
  • I. V. Kuznetsova
  • A. V. Shishkina
  • A. A. Bogdanov
Article

Abstract

Approaches to the synthesis of model compounds based on the tylosin-related macrolides desmycosin and O=mycaminosyltylonolide were developed to study the conformation and topography of the nascent peptide chain in the ribosome tunnel using specially designed peptide derivatives of macrolide antibiotics. A method for selective bromoacetylation of desmycosin at the hydroxyl group of mycinose was developed, which involves preliminary acetylation of mycaminose. The reaction of the 4″-bromoacetyl derivative of the antibiotic with cesium salts of the dipeptide Boc-Ala-Ala-OH and the hexapeptide MeOTr-Gly-Pro-Gly-Pro-Gly-Pro-OH led to the corresponding peptide derivatives of desmycosin. The protected peptides Boc-Ala-Ala-OH, Boc-Ala-Ala-Phe-OH, and Boc-Gly-Pro-Gly-Pro-Gly-Pro-OH were condensed with the C23-hydroxyl group of O-mycaminosyltylonolide.

Key words

tylosin desmycosin O-mycaminosyltylonolide peptide derivatives of macrolides 

Abbreviations

βAla

β-alanine

DCC

N,N′-dicyclohexylcarbodiimide

Des

desmycosin

DIEA

diisopropylethylamine

DMAP

4-dimethylaminopyridine

DNPH

2,4-dinitrophenylhydrazine

Glyc

glycolyl

HBTU

N-hydroxybenzotriazolyluronium hexafluorophosphate

MeOTr

4-monomethoxytrityl

OMT

O-mycaminosyltylonolide

PTC

the peptidyl transferase center

Tyl

tylosin. All amino acids of the L series

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Gale, E.F., Candliffe, E., Reynolds, P.E., Richmond, M.H., and Waring, M.J., The Molecular Basis of Antibiotic Action, London: John Wiley and Sons, 1981.Google Scholar
  2. 2.
    Hansen, J.L., Ippolito, A., Ban, N., Nissen, P., Moore, P.B., and Steitz, A., Mol. Cell, 2002, vol. 10, pp. 117–128.PubMedCrossRefGoogle Scholar
  3. 3.
    Schlunzen, F., Zarivach, R., Harms, J., Bashan, A., Tocilj, A., Albrecht, R., Yonath, A., and Franceschi, F., Nature, 2001, vol. 413, pp. 814–821.PubMedCrossRefGoogle Scholar
  4. 4.
    Schlunzen, F., Harms, J., Franceschi, F., Hansen, H.A., Bartels, H., Zarivach, R., and Yonath, A., Structure, 2003, vol. 11, pp. 329–338.PubMedCrossRefGoogle Scholar
  5. 5.
    Bogdanov, A.A., Mol. Biol. (Moscow), 2003, vol. 37, pp. 1–4.CrossRefGoogle Scholar
  6. 6.
    Sumbatyan, N.V., Korshunova, G.A., and Bogdanov, A.A., Biokhimiya (Moscow), 2003, vol. 68, pp. 1436–1438.Google Scholar
  7. 7.
    Hamill, R.L., Haney, M.E., McGuire, J.M., and Stamper, M.C., US Patent 3 178341, 1965.Google Scholar
  8. 8.
    Morin, R. and Gorman, M., US Patent 3 459 853, 1969.Google Scholar
  9. 9.
    Tanaka, A., Watanabe, A., Tsuchiya, T., and Umezawa, S., J. Antibiot., 1981, vol. 34, pp. 1381–1384.PubMedGoogle Scholar
  10. 10.
    Gisin, B.F., Helv. Chim. Acta, 1973, vol. 56, pp. 1476–1482.CrossRefGoogle Scholar
  11. 11.
    Kirst, H., GB Patent 2 111 497, 1983Google Scholar
  12. 12.
    Kirst, H. and Toth, J., US Patent 4 459 290, 1984.Google Scholar
  13. 13.
    Finkel’shtein, A.V. and Ptitsyn, O.B., Fizika belka: Kurs lektsii (Physics of Proteins: A Course of Lectures), 3rd Ed., Moscow: Knizhnyi dom Universitet, 2005.Google Scholar
  14. 14.
    Konig, W. and Geiger, R., Chem. Ber., 1970, vol. 103, pp. 788–798.PubMedGoogle Scholar
  15. 15.
    Wang, S.S., Gisin, B.F., Winter, D.P., Makofske, R., Kulesha, I.D., Tzograki, C., and Meienhofer, I., J. Org. Chem., 1977, vol. 42, pp. 1286–1290.CrossRefGoogle Scholar
  16. 16.
    Merrifield, R.B., J. Am. Chem. Soc., 1963, vol. 85, pp. 2149–2154.CrossRefGoogle Scholar
  17. 17.
    Kohli, V., Blocker, H., and Koster, H., Tetrahedron Lett., 1980, vol. 21, pp. 2683–2686.CrossRefGoogle Scholar
  18. 18.
    Jian, T., Phanly, T., Busuyek, M., Hou, Y., Or, Y., Qiu, Y., and Vo, N., US Patent 6 753 415 B2, 2003.Google Scholar
  19. 19.
    Fujiwara, T., Watanabe, H., Hirano, T., and Sakakibara, H., GB Patent 2 116 170A, 1983.Google Scholar
  20. 20.
    Sheehan, J.C. and Hess, G.P., J. Am. Chem. Soc., 1955, vol. 77, pp. 1067–1068.CrossRefGoogle Scholar
  21. 21.
    Kessler, H. and Siegmeier, R., Tetrahedron Lett., 1983, vol. 24, pp. 281–282.CrossRefGoogle Scholar
  22. 22.
    McDermott, J.R. and Benoiton, N.L., Can. J. Chem., 1973, vol. 51, pp. 2555–2561.CrossRefGoogle Scholar
  23. 23.
    Knorr, R., Trzeciak, A., Bannwarth, W., and Gillessen, D., Tetrahedron Lett., 1989, vol. 30, pp. 1927–1932.CrossRefGoogle Scholar
  24. 24.
    Medvedkin, V.N., Zabolotskikh, V.F., Permyakov, E.A., Mitin, Yu.V., Sorokina, M.N., and Klimenko, L.V., Bioorg. Khim., 1995, vol. 21, pp. 684–690.PubMedGoogle Scholar
  25. 25.
    Kaiser, E., Colescott, R.L., Bossinger, C.D., and Cook, P.I., Anal. Biochem., 1970, vol. 34, pp. 595–598.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Inc. 2007

Authors and Affiliations

  • G. A. Korshunova
    • 1
  • N. V. Sumbatyan
    • 1
  • N. V. Fedorova
    • 1
  • I. V. Kuznetsova
    • 1
  • A. V. Shishkina
    • 1
  • A. A. Bogdanov
    • 1
  1. 1.Belozersky Research Institute of Physicochemical Biology, Faculty of ChemistryMoscow State UniversityVorob’evy Gory, MoscowRussia

Personalised recommendations