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Amino acid and peptide derivatives of the tylosin family of macrolide antibiotics modified by aldehyde function


Fourteen new functionally active amino acid and peptide derivatives of the antibiotics tylosin, desmycosin, and 5-O-mycaminosyltylonolide were synthesized in order to study the interaction of the growing polypeptide chain with the ribosomal tunnel. The conjugation of various amino acids and peptides with a macrolide aldehyde group was carried out by two methods: direct reductive amination with the isolation of the intermediate Schiff bases or through binding via oxime using the preliminarily obtained derivatives of 2-aminooxy-acetic acid.

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O-(benzotriazolyl)-1,1,3,3-tetramethyluronium hexafluorophosphate






peptidyltransferase center


ribosomal tunnel






  1. Nissen, P., Hansen, J., Ban, N., Moore, P.B., and Steitz, T.A., Science, 2000, vol. 289, pp. 920–930.

    Article  CAS  PubMed  Google Scholar 

  2. Hardesty, B. and Kramer, G., Progr. Nucleic Acid Res. Mol. Biol., 2000, vol. 66, pp. 41–66.

    Article  CAS  Google Scholar 

  3. Bogdanov, A.A., Molekulyarnaya biologiya, 2003, vol. 37, pp. 1–4.

    Google Scholar 

  4. Nakatogawa, H. and Ito, K., Cell, 2002, vol. 109, pp. 629–636.

    Article  Google Scholar 

  5. Jenni, S. and Ban, N., Curr. Opin. Struct. Biol., 2003, vol. 13, pp. 212–219.

    Article  CAS  PubMed  Google Scholar 

  6. Gong, F. and Yanofsky, C., Science, 2002, vol. 297, pp. 1864–1867.

    Article  CAS  PubMed  Google Scholar 

  7. Yonath, A., Annu. Rev. Biochem., 2005, vol. 74, pp. 649–679.

    Article  CAS  PubMed  Google Scholar 

  8. Mankin, A.S., Trends Biochem. Sci., 2006, vol. 31, pp. 11–13.

    Article  CAS  PubMed  Google Scholar 

  9. Schlunzen, R., Zarivach, F., Harms, J., Bashan, A., Tocilj, A., Albrecht, R., Yonath, A., and Franceschi, F., Nature, 2001, vol. 413, pp. 814–821.

    Article  CAS  PubMed  Google Scholar 

  10. Hansen, J., Ippolito, J.A., Ban, N., Nissen, P., Moore, P.B., and Steitz, T.A., Moll. Cell, 2002, vol. 10, pp. 117–128.

    Article  CAS  Google Scholar 

  11. Tenson, T., Lovmar, M., and Ehrenberg, M., J. Mol. Biol., 2003, vol. 330, pp. 1005–1014.

    Article  CAS  PubMed  Google Scholar 

  12. Tenson, T. and Ehrenberg, M., Cell, 2002, vol. 108, pp. 591–594.

    Article  CAS  PubMed  Google Scholar 

  13. Sumbatyan, N.V., Korshunova, G.A., and Bogdanov, A.A., Biokhimiya, 2003, vol. 68, pp. 1436–1438.

    Google Scholar 

  14. Korshunova, G.A., Sumbatyan, N.V., Fedorova, N.V., Kuznetsova, I.V., Shishkina, A.V., and Bogdanov, A.A., Bioorg. Khim., 2007, vol. 33, pp. 235–244 [Russ. J. Bioorg. Chem. (Engl. Tranl.), 2007, vol. 33, pp. 218–226].

    CAS  PubMed  Google Scholar 

  15. McGuire, J., Bonience, W., Higgens, C., Hoehn, M., Stark, W., Westhead, J., and Wolfe, R., Antibiot. Chemother, 1961, vol. 11, pp. 320–327.

    CAS  Google Scholar 

  16. Hamill, R.L., Haney, M.E., McGuire, J.M., and Stamper, M.C., Antibiotics Tylosin and Desmycosin and Derivatives Thereof, US Patent No. 3 178 341, 1965.

  17. Morin, R. and Gorman, M., O-Micaminosyl Tylonolide and Process for the Preparation Thereof, US Patent No. 3459853, 1969.

  18. Vasquez-Laslop, N., Thum, C., and Mankin, A.S., Mol. Cell, 2008, vol. 30, pp. 190–202.

    Article  Google Scholar 

  19. Debono, M., Willard, K.E., Kirst, H.A., Wind, J.A., Crouse, G.D., Tao, E.V., Vicenzi, J.T., Counter, F.T., Ott, J.L., and Ose, E.E., J. Antibiot., 1989, vol. 42, pp. 1253–1267.

    CAS  PubMed  Google Scholar 

  20. Kirst, H.A., Willard, K.E., Debono, M., Toth, J.E., Truedell, B.A., Leeds, J.P., Ott, J.L., Felty-Duckworth, A.M., Counter, F.T., Ose, E.E., Crouse, G.D., Tustin, J.M., and Omura, S., J. Antibiot., 1989, vol. 42, pp. 1673–1683.

    CAS  PubMed  Google Scholar 

  21. Mutak, S., Marsik, N., Kramaric, M.D., and Pavlovic, D., J. Med. Chem., 2004, vol. 47, pp. 411–431.

    Article  CAS  PubMed  Google Scholar 

  22. Lundi, K.M. and Vu, C.B., Amide derivatives of 16-Membered Ring Antibiotic Macrolides, US Patent No. 5716939, 1998.

  23. Yang, D., Ng, F.F., and Li, Z.J., J. Am. Chem. Soc., 1996, vol. 118, pp. 9794–9795.

    Article  CAS  Google Scholar 

  24. Woolhead, C.A., McCormick, P.J., and Johnson, A.E., Cell, 2004, vol. 116, pp. 725–736.

    Article  CAS  PubMed  Google Scholar 

  25. Lu, J. and Deutsch, C., Nat. Struct. Mol. Biol., 2005, vol. 12, pp. 1123–1129.

    Article  CAS  PubMed  Google Scholar 

  26. Finkel’shtein, A.V. and Ptitsin, O.B., Fizika belka: Kurs lektsii s tsvetnymi i stereoskopicheskimi illyustratsiyami i zadachami: 3-e izd (Protein Physics: A Course of Lectures with Color Stereoscopic Illustrations and Problems, 3rd ed.), Moscow: KDU, 2005.

    Google Scholar 

  27. Bonora, G.M., Nisato, D., and Toniolo, C., Makromol. Chem., 1975, vol. 176, pp. 2535–2545.

    Article  CAS  Google Scholar 

  28. Lorenzi, G.P., Rizzo, V., Thoresen, F., and Tomasic, L., Macromolecules, 1979, vol. 12, pp. 870–874.

    Article  CAS  Google Scholar 

  29. Han, S.Y. and Kim, Y.A., Tetrahedron, 2004, vol. 60, pp. 2447–2467.

    Article  CAS  Google Scholar 

  30. Pshenichnikova, A.B., Karnaukhova, E.N., Mitsner, B.I., and Shchvets, V.I., Bioorg. Khim., 1996, vol. 10, pp. 852–855.

    Google Scholar 

  31. Debono, M. and Kirst, H.A., C-20-Dihydro-Deoxy-(Cyclic Amino)-Derivatives of Macrolide Antibiotics, US Patent No. 4820695, 1989.

  32. Rossi, C., Donati, A., Picci, M.P., Sansoni, M.R., Corbini, G., and Corti, P., Magn. Reson. Chem., 1992, vol. 30, pp. 954–957.

    Article  CAS  Google Scholar 

  33. Naranda, A. and Lopotar, N., J. Antibiot., 1999, vol. 52, pp. 68–70.

    CAS  PubMed  Google Scholar 

  34. RTS 100 E. coli HY Kit. Instruction Manual, Mannhein: Roche Diagnostics, 2007.

  35. Dinos, G., Wilson, D.N.., Teraoka, Y., Szaflarski, W., Fucini, P., Kalpaxis, D., and Nierhaus, K.H., Molecular Cell, 2004, vol. 13, pp. 113–124.

    Article  CAS  PubMed  Google Scholar 

  36. Harmsen, D., Erker, G., Froehlich, R., and Kehr, G., Eur. J. Inorg. Chem., 2002, pp. 3156–3171.

  37. Shields, J.E., McDowell, S.T., Pavlos, J., and Gray, G.R., J. Am. Chem. Soc., 1968, vol. 90, pp. 3549–3556.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to N. V. Sumbatyan.

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Original Russian Text © N.V. Sumbatyan, I.V. Kuznetsova, V.V. Karpenko, N.V. Fedorova, V.A. Chertkov, G.A. Korshunova, A.A. Bogdanov, 2010, published in Bioorganicheskaya Khimiya, 2010, Vol. 36, No. 2, pp. 265–276.

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Sumbatyan, N.V., Kuznetsova, I.V., Karpenko, V.V. et al. Amino acid and peptide derivatives of the tylosin family of macrolide antibiotics modified by aldehyde function. Russ J Bioorg Chem 36, 245–256 (2010).

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Key words

  • macrolides
  • chemical modification
  • reductive amination
  • oximes
  • peptide derivatives
  • tylosin
  • desmycosin
  • 5-O-mycaminosyltylonolide