Wileman T E, Foster R L, Elliott P N
J Pharm Pharmacol. 1986 Apr;38(4):264-71. doi: 10.1111/j.2042-7158.1986.tb04564.x.
Oxidized dextrans of increasing molecular weight were bound covalently to Erwinia carotovora asparaginase. The resulting conjugates retained 50% of their enzyme activity and showed marked resistance to proteolysis by trypsin and chymotrypsin and inactivation by asparaginase-specific antibody. When tested in-vivo, the larger molecular weight conjugates showed prolonged circulatory survival in both immune and non-immune animals and failed to elicit full type III hypersensitivity or anaphylactic reactions when injected into sensitized guinea-pigs. Rabbits could tolerate multiple doses of the asparaginase conjugate without developing an immunity to the enzyme. A conjugate showing increased circulatory half-life and lowered antigen reactivity should have therapeutic potential.
将分子量不断增加的氧化葡聚糖共价结合到胡萝卜软腐欧文氏菌天冬酰胺酶上。所得的偶联物保留了50%的酶活性，并对胰蛋白酶和糜蛋白酶的蛋白水解作用以及天冬酰胺酶特异性抗体的失活作用表现出显著抗性。在体内试验时，较大分子量的偶联物在免疫和非免疫动物体内均显示出延长的循环存活时间，并且当注射到致敏豚鼠体内时，未能引发完全的III型超敏反应或过敏反应。兔子能够耐受多次剂量的天冬酰胺酶偶联物而不会对该酶产生免疫。一种显示出延长的循环半衰期和降低的抗原反应性的偶联物应具有治疗潜力。
