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

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 <SC>l</SC>-asparaginase was chemically modified with these copolymers. The modified <SC>l</SC>-asparaginase exhibited the complete loss of antigenicity towards anti-asparaginase serum from rabbit. The highest enzyme activity of the modified <SC>l</SC>-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 <SC>l</SC>-asparaginase was quickly cleared from the plasma of rabbits (half-life time: t<INF>1/2</INF>=1.2 hr), whereas the modified enzyme showed prolonged clearance from plasma (t<INF>1/2</INF>=53 hr). © 1997 John Wiley & Sons, Ltd.