Antibody-ricin conjugates: a method of linkage which blocks the galactose binding site of ricin.

Antibody-ricin conjugates: a method of linkage which blocks the galactose binding site of ricin.
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抗体-蓖麻毒素缀合物:一种阻断蓖麻毒素半乳糖结合位点的连接方法。

DOI:
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发表时间:
1984
期刊:
Behring Institute Mitteilungen
影响因子:
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通讯作者:
P. Thorpe
P. Thorpe
中科院分区:
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文献类型:
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作者:
B. Foxwell;W. Ross;P. Thorpe

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已经使用硫醚键构建了单克隆抗体抗Thy 1:1(OX 7)和蓖麻毒素的缀合物,使得蓖麻毒素不再能够结合琼脂糖凝胶或去唾液酸胎球蛋白。发现这些缀合物对表达Thy 1:1的AKR-A细胞具有很强的毒性,而它们对表达Thy 1:2的EL 4细胞几乎没有毒性。通过比较,保留半乳糖结合能力的OX 7-蓖麻毒素缀合物对EL 4细胞仍然具有高毒性,并且这种毒性被乳糖拮抗。构建了由W3/25单克隆抗体制备的第二种缀合物。失去琼脂糖结合能力的W3/25-蓖麻毒素缀合物对表达W3/25抗原的大鼠T-白血病细胞具有毒性。这与完全无活性的二硫键连接的W3/25-蓖麻毒素A链缀合物形成鲜明对比,表明B链在A链进入胞质溶胶的膜转运中的作用不依赖于半乳糖识别。
Conjugates of the monoclonal antibody anti-Thy 1:1 (OX7) and ricin have been constructed, using a thioether bond, such that the ricin no longer can bind Sepharose or asialofetuin. These conjugates were found to be very toxic to Thy 1:1 expressing AKR-A cells whereas they showed little toxicity to Thy 1:2 expressing EL4 cells. By comparison, OX7-ricin conjugates which retained galactose-binding capability were still highly toxic to EL4 cells and this toxicity was antagonized by lactose. A second conjugate made from the W3/25 monoclonal antibody was constructed. The W3/25-ricin conjugate which had lost Sepharose-binding capacity was toxic to W3/25 antigen-expressing rat T-leukaemia cells. This is in sharp contrast to the disulphide linked W3/25-ricin A-chain conjugate which is totally inactive, suggesting that the role of the B-chain in membrane transport of the A-chain into the cytosol is independent of galactose recognition.