TY - JOUR T1 - Physical and Biological Properties of Acetamidino-, β-Dimethylaminopropionamidino-, and Maleyl-L-Asparaginase JF - Molecular Pharmacology JO - Mol Pharmacol SP - 534 LP - 541 VL - 9 IS - 4 AU - LARRY E. HARE AU - ROBERT E. HANDSCHUMACHER Y1 - 1973/07/01 UR - http://molpharm.aspetjournals.org/content/9/4/534.abstract N2 - Modification of Escherichia coli L-asparaginase (EC 3.5.1.1) with maleic anhydride, ethyl acetimidate, or methyl β-dimethylaminopropionimidate resulted in enzyme derivatives with altered isoelectric points. Catalytic activity was not significantly changed by these modifications; however, an unexpected covalent cross-linking of enzyme subunits was seen in β-dimethylaminopropionamidino-asparaginase. Although immunological studies in vitro indicated minor alterations in cross-reactivity between the native and modified enzymes, no immunological differences were apparent in vivo. The biological half-life of these enzymes increases with increasing isoelectric point, and this relationship was associated with enhanced therapeutic effectiveness in leukemic mice. ACKNOWLEDGMENTS The authors gratefully acknowledge the technical assistance of Mrs. Celeste Grant and the collaboration of Mr. Robert Peterson on portions of this work. ER -