3-(2-pyridyldithio)propionic acid hydrazide as a cross-linker in the formation of liposome-antibody conjugates
3-(2-pyridyldithio)propionic acid hydrazide as a cross-linker in the formation of liposome-antibody conjugates
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DOI：
10.1021/bc960036
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发表时间：
1996-07-01
影响因子：
4.7
通讯作者：
Buchkowsky, SS
中科院分区：
文献类型：
--
作者：
Ansell, SM;Tardi, PG;Buchkowsky, SS
脂质体抗体结合物作为一种针对特定组织的药物靶向手段具有潜在的实用价值。以3-(2-吡啶二硫)丙酸肼(PDPH)为交联剂，建立了一种新的抗体偶联马来酰亚胺脂质体的方法。过碘酸盐氧化的抗体用PDPH处理，得到一种肼类化合物。用DTT去保护产生一种硫化抗体，然后将其连接到含有N-[4-(p-maleidophenyl)butyryl]-1，2-sn-distearoylphosphatidylethanolamine.的脂质体上脂质体-抗体结合物的体外性质与传统的3-(2-吡啶二硫)丙酸N-羟基琥珀酰亚胺(SPDP)法形成的结合物相似，但在循环中清除较慢。PDPH方案为SPDP提供了一种可行的替代方案，特别是对于对胺修饰敏感的抗体。
Liposome antibody conjugates are potentially useful as a means of targeting drugs to specific tissues. A new protocol for the conjugation of IgG to maleimide-containing liposomes was developed using 3-(2-pyridyldithio)propionic acid hydrazide (PDPH) as a cross-linker. Periodate-oxidized antibody was treated with PDPH to yield a hydrazone derivative. Deprotection with DTT produced a thiolated antibody which was then conjugated to liposomes containing N-[4-(p-maleidophenyl)butyryl]-1,2-sn-distearoylphosphatidylethanolamine. The Liposome-antibody conjugates were found to have in vitro properties similar to those of conjugates formed by the traditional 3-(2-pyridyldithio)propionic acid N-hydroxysuccinimide ester (SPDP) protocol but were cleared less rapidly in circulation. The PDPH protocol presents a viable alternative to SPDP, particularly for antibodies sensitive to amine modification.