Site-Specific Traceless Coupling of Potent Cytotoxic Drugs to Recombinant Antibodies for Pharmacodelivery
Site-Specific Traceless Coupling of Potent Cytotoxic Drugs to Recombinant Antibodies for Pharmacodelivery
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DOI：
10.1021/ja211589m
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发表时间：
2012-04-04
影响因子：
15
通讯作者：
Neri, Dario
中科院分区：
文献类型：
--
作者：
Casi, Giulio;Huguenin-Dezot, Nicolas;Neri, Dario
考虑到醛脱氢酶过度表达是癌症干细胞的特征，醛类药物正引起越来越多的研究兴趣。在这里，我们描述了一种含有醛基的新型强效药物与重组抗体的无痕位点特异性偶联，重组抗体经过工程改造，在其 N 末端显示半胱氨酸残基，或在 C 末端显示 1,2-氨基硫醇。所得化学成分确定的抗体-药物缀合物代表了第一个例子，其中噻唑烷键用于细胞毒性剂的靶向递送和释放。
Aldehyde drugs are gaining increasing research interest, considering that aldehyde dehydrogenases overexpression is characteristic of cancer stem cells. Here, we describe the traceless site-specific coupling of a novel potent drug, containing an aldehyde moiety, to recombinant antibodies, which were engineered to display a cysteine residue at their N-terminus, or a 1,2-aminothiol at their C-terminus. The resulting chemically defined antibody-drug conjugates represent the first example in which a thiazolidine linkage is used for the targeted delivery and release of cytotoxic agents.