Sato P, Lindemann D
J Appl Biochem. 1985 Aug-Oct;7(4-5):323-31.
Studies were carried out to assess the prospects of adapting an enzyme administration procedure developed with rat liver gulonolactone oxidase to other enzymes of therapeutic interest. The enzyme is administered intraperitoneally as the glutaraldehyde-reacted immunoprecipitate. A gulonolactone oxidase from a different source, chicken kidney, also shows catalytic capability following administration. This finding suggests that other enzymes modified by this procedure might also act in vivo. Four out of five enzymes tested (asparaginase, serum cholinesterase, rat and chicken gulonolactone oxidases) have significant catalytic activity and relatively minor changes in affinity for substrate after the modification, and only one (histidase) is inactivated by the modification. Analysis of immunoprecipitates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of these enzymes indicates that they consist largely of enzyme and immunoglobulin G. All five of these modified enzymes are not toxic even with repetitive administrations whereas unmodified asparaginase is allergenic to a majority of guinea pigs tested. The modification described is very simple and rapid and is, therefore, a practical means of preparing certain enzymes for therapeutic administration.
开展了多项研究，以评估将一种用大鼠肝脏古洛糖酸内酯氧化酶开发的酶给药程序应用于其他具有治疗意义的酶的前景。该酶以戊二醛反应的免疫沉淀物形式腹腔注射给药。来自不同来源（鸡肾）的古洛糖酸内酯氧化酶在给药后也显示出催化能力。这一发现表明，通过该程序修饰的其他酶也可能在体内发挥作用。所测试的五种酶中有四种（天冬酰胺酶、血清胆碱酯酶、大鼠和鸡的古洛糖酸内酯氧化酶）在修饰后具有显著的催化活性，且对底物的亲和力变化相对较小，只有一种（组氨酸酶）在修饰后失活。通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳对这些酶的免疫沉淀物进行分析表明，它们主要由酶和免疫球蛋白G组成。所有这五种修饰后的酶即使重复给药也无毒，而未修饰的天冬酰胺酶对大多数受试豚鼠具有致敏性。所述修饰非常简单快捷，因此是制备某些用于治疗给药的酶的实用方法。
