Enzyme modification by MPEG with an amino acid or peptide as spacer arms


A method for the modification of enzymes by MPEG carrying an amino acid or peptide as a spacer arm is described and tested with aliphatic or aromatic side chains amino acids. The procedure involves MPEG activation byp-nitrophenylchloroformate for the amino acid or peptide coupling that is in turn activated for the protein binding.

The advantage of the method resides in the possibility to introduce proper reporter groups between the polymer and the protein as norleucine for a direct evaluation of the bound polymer chains, tryptophan for structural studies of the polymer-protein adduct, and radioactive amino acid for pharmacokinetic investigations.

The method was positively tested with arginase, ribonuclease, and superoxide dismutase as enzymes of therapeutic value.

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  1. 1.

    Abuchowski, A. and Davis, F. F. (1981), inEnzymes as Drugs, Holcenberg, J. S. and Roberts, J., ed., Wiley & Sons, pp 367-384.

  2. 2.

    Conforti, A., Franco, L., Milanino, R., Velco, G. P., Boccu, E., Largajolli, R., Schiavon, O. and Veronese, F. M. (1987),Pharmacol. Research Comunic. 19, 287.

    Article  CAS  Google Scholar 

  3. 3.

    Veronese, F. M. (1989),Chimica Oggi 7, 53.

    CAS  Google Scholar 

  4. 4.

    Yoshinga, K. and Harris, J. M. (1989),J. Bioactive Compatible Polymers 4, 17.

    Article  CAS  Google Scholar 

  5. 5.

    Kopecek, J. and Duncan, R. (1987),J. Controlled Release 6, 315.

    Article  CAS  Google Scholar 

  6. 6.

    Crook, E. M., Mathias, A. P. and Rabin, B. R. (1960),J. Biochem. 74, 234.

    CAS  Google Scholar 

  7. 7.

    Paoletti, F., Aldinucci, D., Mocali, A. and Caparrini, A. (1986),Anal. Biochem. 154, 536.

    Article  CAS  Google Scholar 

  8. 8.

    Snyder, S. L. and Sabocinsky, P. Z. (1975),Anal. Biochem. 64, 248.

    Article  Google Scholar 

  9. 9.

    Sims, G. E. C. and Snape, T. J. (1980),Anal. Biochem. 107, 60.

    Article  CAS  Google Scholar 

  10. 10.

    Visco, C, Benassi, C. A., Veronese, F. M., and Miglioli, P. A. (1987),II Farmaco 42, 549.

    CAS  Google Scholar 

  11. 11.

    Caliceti, P., Schiavon, O., Mocali, A., and Veronese, F. M. (1989),II Farmaco 44, 711.

    CAS  Google Scholar 

  12. 12.

    Veronese, F.M., Caliceti, P., Pastorino, A., Schiavon, O., Sartore, L., Banci, L., and Monsu Scolaro, L. (1989),J. Controlled Release 10, 145.

    Article  CAS  Google Scholar 

  13. 13.

    Schiavon, O. et al. in preparastion.

  14. 14.

    Joppich, M., and Luisi, P. L. (1979),Makromol. Chem. 180, 1381.

    Article  CAS  Google Scholar 

  15. 15.

    Brand, L. and Whithold, B. (1967),Methods Enzymol. 11, 776.

    Article  CAS  Google Scholar 

  16. 16.

    Veronese, F. M., Sartore, L., Caliceti, P., Schiavon, O., Ranucci, E., and Ferruti, P. (1989),J. Bioactive Compatible Polymers (in press).

  17. 17.

    Hemant, N. J. (1988),Pharmaceutical Technology 12, 118.

    Google Scholar 

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Correspondence to Luciana Sartore or Paolo Caliceti or Oddone Schiavon or Francesco M. Veronese.

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Sartore, L., Caliceti, P., Schiavon, O. et al. Enzyme modification by MPEG with an amino acid or peptide as spacer arms. Appl Biochem Biotechnol 27, 45–54 (1991). https://doi.org/10.1007/BF02921514

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Index Entries

  • Surface protein modifications
  • monomethoxypolyethylene glycol
  • amino acid or peptide derivatized MPEG
  • enzymes for therapy
  • arginase
  • ribonucleases and superoxide dismutase