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

Vladimír ure

Tomá Etrych

Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsk Sq. 2, 162 06 Prague 6, Czech Republic

Karel Ulbrich

Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsk Sq. 2, 162 06 Prague 6, Czech Republiculbrich{at}imc.cas.cz

Takashi Hirano

Institute of Molecular and Cell Biology, National Institute of Advanced Industrial Science and Technology, Tsukuba-Higashi 1-1-1 305-8566 Japan

Tadashi Kondo

Takeshi Todoroki

Institute of Clinical Medicine, University of Tsukuba, 305-8575 Tsukuba, Japan

Markéta Jelínková

Blanka íhová

Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeská 1083, 14220 Prague 4, Czech Republic

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.

Journal of Bioactive and Compatible Polymers, Vol. 17, No. 2, 105-122 (2002)
DOI: 10.1106/088391102024442


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