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Abstract

The synthesis of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers and semi-telechelic polymers (PHPMA) conjugates superoxide dismutase (SOD) is described. The polymer was conjugated with SOD by means ofnondegradable or degradable oligopeptide spacers randomly distributed along the polymer backbone. A second type ofconjugation, to a semi-telechelic polymer, poly(HPMA), (PHPMA) containing reactive chain end groups, with the SOD amino groups formed star structures. Physicochemical properties of the conjugates, such as temperature stability and stability to oxidation with hydrogen peroxide, were studied and compared to native SOD; an increase in temperature stability by the conjugates and an increase in stability towards oxidation with hydrogen peroxide was observed. The in vivo biological evaluation of PHPMA–SOD conjugates showed a significant decrease in immunogenicity compared to free SOD. A preliminary in vivo study of ischemic/reperfusion injury, revealed significantly more pronounced protective effects by PHPMA–SOD conjugates in comparison with the free SOD.

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References

1. McCord, J.M. and Fridovich, I. (1969). J. Biol. Chem., 244: 6049-6049.

2. Park, D.A. , Bulkley, G.B. and Granger, D.N. (1983). Surgery, 94: 415-415.

3. Kojima, Y. , Akaike, T. , Sato, K. , Maeda, H. and Hirano, T. (1996). J. Bioact. Compat. Pol., 11: 169-169.

4. McCord, J.M. (1985). New Engl. J. Med., 312: 159-159.

5. Castillo, M. , Toledo-Pereyra, L.H. , Shapiro, E. , Guerra, E. , Prough, D. and Frantzis, P. (1990). Transplant. Proc., 22: 490-490.

6. Monfardini, C. and Veronese, F.M. (1998). Bioconjugate Chem., 9: 418-418.

7. Caliceti,P. , Schiavon, O. , Morpurgo,M. , Veronese, F.M. , Sartore, L. , Ranucci, E. and Ferruti, P. (1995). J. Bioact. Compat. Pol., 10: 103-103.

8. Hirano, T. , Todoroki, T. , Kato, S. , Yamamoto, H. , Caliceti, P. , Veronese, F.M. , Maeda, H. and Ohashi, S. (1994). J. Controlled Rel., 28: 203-203.

9. Caliceti, P. , Schiavon, O. , Hirano, T. , Ohashi, S. and Veronese, F.M. (1996). J. Controlled Rel., 39: 27-27.

10.

10. Kondo, T. , Terajima, H. , Todoroki, T. , Hirano, T. , Ito, Y. , Usia, T. and Messmer, K. (1999). J. Surgical Res., 85: 26-26.

11.

11. White, C.W. , Jackson, J.H. , Abuchowski, A. , Kazo, G.M. , Mimmack, R.F. , Berger, E.M. , Freeman, B.A. , McCord, J.M. and Repine, J.E. (1989). J. Appl. Physiol., 66: 584-584.

12.

12. Nucci, M.L. , Olejarczyk, J. and Abuchowski, A. (1986). J. Free Radicals in Biology and Medicine, 2: 321-321.

13.

13. Cheng, T.L. , Chen, B.M. , Chan, L.Y. , Wu, P.Y. , Chern, J.W. and Roffler, S.R. (1997). Cancer Immunol. Immunother., 44: 305-305.

14.

14. Oupický, D. , Ulbrich, K. and Říhová, B. (1999). J. Bioact. Compat. Polym., 14: 213-213.

15.

15. Ulbrich, K. , Strohalm, J. , Plocová, D. , Oupický, D. , Šubr, V. , Souček, J. , Poučková, P. and Matoušek, J. (2000). J. Bioact. Compat. Polym., 15:4-4.

16.

16. Swart, P.J. , Hirano, T. , Kuipers, M.E. , Ito, Y. , Smit, C. , Hashida, M. , Nishikawa, M. , Beljaars, L. , Meijer, D.K.F. and Poelstra, K. (1999). J. Hepatology, 31: 1034-1034.

17.

17. Ulbrich, K. , Šubr, V. , Strohalm, J. , Plocová, D. , Jelínková, M. and Říhová, B. (2000). J. Controll. Release, 64: 63-63.

18.

18. Říhová, B. , Jelínková, M. , Strohalm, J. , Šubr, V. , Plocová, D. , Hovorka, O. , Novák, M. , Plundrová, D. , Germano, Y. and Ulbrich, K. (2000). J. Control. Rel., 64: 241-241.

19.

19. Říhová, B. and Kopeček, J. (1985). J. Controll. Release, 2: 289-289.

20.

20. Souček, J. , Poučková, P. , Zadinová, M. , Hloušková, D. , Plocová, D. , Strohalm, J. , Hrkal, Z. , Olear, T. and Ulbrich, K. (2001). Neoplasma, 48:128-128.

21.

21. Kopeček, J. , Rejmanová, P. and Chytrý, V. (1981). Makromol. Chem., 182: 799-799.

22.

22. Rejmanová, P. , Kopeček, J. , Pohl, J. , Baudyš, M. and Kostka, V. (1983). Makromol. Chem., 184: 2009-2009.

23.

23. Ulbrich, K. , Pechar, M. , Strohalm, J. , Šubr, V. and Říhová, B. (1997). Macromol. Symp., 118: 577-577.

24.

24. Snyder, S. and Sobocinski, P. (1975). Anal. Biochem., 64: 284-284.

25.

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

26.

26. Říhová, B. , Baudyš, M. , Tlaskalová, H. , Říhová, H. and Kim, S.W. (1994). J. Clin. Lab. Immunol., 44: 191-191.

27.

27. Kondo, T. , Okamoto, S. , Todoroki, T. , Hirano, T. , Schidberg, F.W. and Messmer, K. (1998). Eur. Surg. Res., 30: 252-252.

28.

28. Adkins, B. , Bu, Y. , Cepero, E. and Perez, R. (2000). J. Immunol., 164: 2347-2347.

29.

29. Noda, J. , Otagiri, M. , Akaike, T. and Maeda, H. (1996). J. Pharmacol. Exp. Ther., 279: 162-162.

30.

30. Kojima, Y. , Haruta, A. , Imai, T. , Otagiri, M. and Maeda, H. (1993). Bioconjugate Chemistry, 4: 490-490.

31.

31. Somack, R. , Saifer, M.G. and Williams, L.D. (1991). Free Radical Res. Commun., 12: 553-553.

32.

32. Sehon, A.H. (1982). Prog. Allergy, 32: 161-161.

33.

33. Wilkinson, I. , Jackson, C.J.C. , Lang, G.M. , Holfordstrevens, V. and Sehon, A.H. (1987). J. Immunol., 139: 326-326.

34.

34. Chen, Y. , Takata, M. , Maiti, P.K. , Mohapatra, S. , Mohapatra, S.S. and Sehon, A.H. (1994). J. Immunol., 152:3-3.

Synthesis and Properties of Poly[N-(2-Hydroxypropyl) Methacrylamide] Conjugates of Superoxide Dismutase

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