l-asparaginase is a chemotherapy agent in the treatment of childhood leukemia. l-asparaginase has several side effects and a short blood half-life in patients. Chemical modification of l-asparaginase can decrease its side effects and improve its pharmacokinetic properties. The aim of this project was twofold: to chemically modify l-asparaginase with carboxymethyl dextran via carbodiimide cross linker, and to evaluate and compare the biochemical and structural properties of the native and modified enzymes. Chemical modification was done at 25 °C, in 0.1 M phosphate buffer, pH 7.2, and in the presence of N-hydroxysuccinimide and carbodiimide. Electrophoresis and free amino groups determination confirmed the chemical modification. Biochemical studies showed that the chemical modification could result in higher specific activity and stability of the modified enzyme. Structural studies further confirmed the chemical modification and revealed conformational changes in the modified enzyme. Taken together, the results showed that chemical modification with carboxymethyl dextran brings about improvement of biochemical properties through several changes in the structural attributes of l-asparaginase and might enhance its applicability in the treatment of childhood leukemia.
Keywords: Carbodiimide; Carboxymethyl dextran; Chemical modification; L-asparaginase; Leukemia.
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