Chemical modification of <i>E. coli</i> <scp>L</scp> ‐asparaginase with polyethylene glycol grafted vinylpyrrolidone–maleic anhydride copolymer

Abstract

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.