PHYSICOCHEMICAL AND BIOLOGICAL PROPERTIES OF MONOFUNCTIONAL HYDROXY TERMINATING POLY(N-VINYLPYRROLIDONE) CONJUGATED SUPEROXIDE-DISMUTASE

Monofunctional hydroxy-terminated poly(N-vinylpyrrolidone) was obtaine d by radical polymerization in the presence of isopropoxyethanol for p rotein surface modification. Superoxide dismutase was modified to vari ous degrees by reaction with PVP-OH activated by 4-nitrophenyl chlorof ormate with high retention of enzymatic activity. All the polymer-enzy me conjugates showed increased body residence time after intravenous i njection in rats with respect to the native enzyme. The residence time depended upon the number of bound polymer chains. PVP was found to af fect the pharmacokinetic properties of the enzyme after subcutaneous, intramuscular and intraperitoneal administration. The antigenicity of superoxide dismutase was reduced to one third following modification, while its immunogenicity after intravenous, subcutaneous and intraperi toneal injection totally disappeared. The conjugates exhibited increas ed solubility in organic solvents and increased stability towards ther mal denaturation, whereas changes in the structural properties were ob served by circular dichroism measurements.