Abstract
The discovery of a novel superoxide dismutase (SOD) mimic which demonstrates SOD activity, chemical stability in H2O2 solution and long half-life in circulation is reported. The SOD mimic consists of a manganese porphyrin (MnP) with SOD activity and a polymer (poly (styrene-co-maleic anhydride); SMA) with biological characteristics. The SOD activity of SMA-MnP at pH = 8.1 measured using the stopped-flow kinetic analysis technique to monitor the decay of superoxide directly was 1.1 (± 0.1) × 106 M-1 sec-1. It is postulated that the reduction by O2·− of the oxidized SMA-Mn(III) is slow, while the oxidation of the reduced SMA-Mn(II) by O2·− is very fast. The retention times of SMA-MnP in the circulation of rabbits were determined. In vivo, SMA-MnP that binds to the warfarin site on albumin showed an enhanced half-life in the circulation. Additionally, in vitro SMA-MnP indicated an excellent stability to H2O2. Copyright © 1999 John Wiley & Sons, Ltd.
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