CHEMICAL MODIFICATION OF L-ASPARAGINASE WITH N,O-CARBOXYMETHYL CHITOSAN AND ITS EFFECTS ON PLASMA HALF-LIFE AND OTHER PROPERTIES

E. coli L-asparaginase, an antitumor enzyme, was chemically modified w ith N,O-carboxymethyl chitosan to lower its antigenicity and increase its plasma half-life. The results showed that the modified L-asparagin ase has almost the same apparent Km value as that of native enzyme. Th e modified L-asparaginase also showed a higher protease stability agai nst trypsin and alpha-chymotrypsin. After being modified, the enzyme e xhibited the complete loss of antigenicity towards antiasparaginase se rum. In addition, the higher the molecular weight of modifying reagent s, the better the effects on reduction of antigenicity. When tested in vivo, the plasma half-life of the modified enzyme (t(1/2) = 40 h) was over 33 times longer than that of the native enzyme (t(1/2) = 1.2 h).