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E. coli L-asparaginase was modified with N, O-carboxymehtyl chitosan in the presence of normal product L-aspartic acid, which protected the active site of the enzyme. The modified enzyme remained high catalytic activity, showed greater stability against trypsin and α-chymotrypsin, but lost its activity more rapidly at high temperature (>45 °C) than did the native enzyme. When tested in vivo, the plasma half-life of the modified enzyme (t1/2 = 40 hr) was over 33 times longer than that of the native enzyme (t1/2 = 1.6 hr). The results showed that the modified L-asparaginase may be much more useful than did the native enzyme for clinical treatments of tumors.

A series of polyethylene glycol grafted vinylpyrrolidone–maleic anhydride copolymers [P(VMP)] was synthesized by radical copolymerization of vinylpyrrolidone, maleic anhydride and polyethylene glycol maleic acid monoester. Escherichia coli l‐asparaginase was chemically modified with these copolymers. The modified l‐asparaginase exhibited the complete loss of antigenicity towards anti‐asparaginase serum from rabbit. The highest enzyme activity of the modified l‐asparaginase without antigenicity was retained by 59% of the nonmodified one. The modified enzyme was also more resistant to trypsin in vitro. When tested in vivo, the native l‐asparaginase was quickly cleared from the plasma of rabbits (half‐life time: t1/2=1.2 hr), whereas the modified enzyme showed prolonged clearance from plasma (t1/2=53 hr). © 1997 John Wiley & Sons, Ltd.

A series of polyethylene glycol grafted vinylpyrrolidone–maleic anhydride copolymers [P(VMP)] was synthesized by radical copolymerization of vinylpyrrolidone, maleic anhydride and polyethylene glycol maleic acid monoester. Escherichia coli l-asparaginase was chemically modified with these copolymers. The modified l-asparaginase exhibited the complete loss of antigenicity towards anti-asparaginase serum from rabbit. The highest enzyme activity of the modified l-asparaginase without antigenicity was retained by 59% of the nonmodified one. The modified enzyme was also more resistant to trypsin in vitro. When tested in vivo, the native l-asparaginase was quickly cleared from the plasma of rabbits (half-life time: t1/2=1.2 hr), whereas the modified enzyme showed prolonged clearance from plasma (t1/2=53 hr). © 1997 John Wiley & Sons, Ltd.