PT  - JOURNAL ARTICLE
AU  - LARRY E. HARE
AU  - ROBERT E. HANDSCHUMACHER
TI  - Physical and Biological Properties of Acetamidino-, β-Dimethylaminopropionamidino-, and Maleyl-L-Asparaginase
DP  - 1973 Jul 01
TA  - Molecular Pharmacology
PG  - 534--541
VI  - 9
IP  - 4
4099  - http://molpharm.aspetjournals.org/content/9/4/534.short
4100  - http://molpharm.aspetjournals.org/content/9/4/534.full
SO  - Mol Pharmacol1973 Jul 01; 9
AB  - 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.