用三种不同的异型双功能交联剂把单抗和完整蓖麻毒素连接起来,经适当纯化获得了高活性免疫毒素(ITs),体外试验中蛋白质合成抑制50%的浓度IC50达到2.7×10-12mol/L.以二硫键连接的ITs比硫醚键连接的ITs细胞毒性高5—10倍(P<0.05),而硫醚键连接的ITs在动物体内代谢慢1倍,且其原型药物维持时间更长,稳定性更好。两类ITs在体内的代谢产物也不相同。
A monoclonal antibody (H65) was coupled to ricin using three different cross-agents respectively. Immunotoxins (ITs) with greater cytotoxic potency were obtained through a proper scheme. The ITs reduced the 3H-leucine incorporation of Molt-4 cells by 50% at a concentration (IC50) of 2.7×10-12mol/L. ITs prepared with disulfide bond is 5—10 fold more cytotoxic in vitro than those prepared with thioether bond. The speed of metabolism of the latter in vivo is two times slower than that of the former. Because these two kinds of ITs have different degradation products, their metabolism pathways in vivo may be different also.
汲言山,贺永怀,陈兴,赵薇薇,沈倍奋.不同交联方法制备的免疫毒素及其体内外特性[J].生物化学与生物物理进展,1991,18(6):443-447
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