NOVEL DOXORUBICIN-MONOCLONAL ANTICARCINOEMBRYONIC ANTIGEN-ANTIBODY IMMUNOCONJUGATE ACTIVITY IN-VITRO
NOVEL DOXORUBICIN-MONOCLONAL ANTICARCINOEMBRYONIC ANTIGEN-ANTIBODY IMMUNOCONJUGATE ACTIVITY IN-VITRO
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DOI：
10.1016/0968-0896(95)00126-2
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发表时间：
1995-10-01
影响因子：
3.5
通讯作者：
GALLANT, M
中科院分区：
文献类型：
--
作者：
LAU, A;BERUBE, G;GALLANT, M
用五种不同的异双功能试剂修饰多柔比星以产生含有3 ′-N-酰胺或C-13腙与马来酰亚胺连接的药物类似物。本文报道了两种新试剂4-马来酰亚胺苯甲酰肼三氟乙酸盐（13）和N-（4-马来酰亚胺苯甲酰）-6-氨基己酰肼三氟乙酸盐（14）的合成和表征。所有Dox马来酰亚胺衍生物通过Michael加成反应与硫醇化抗癌胚抗原单克隆抗体11-285-14偶联。使用抗原阳性和抗原阴性细胞系的组合，用MTT测定证明抗体定向的细胞毒性。从Dox制备的免疫缀合物。3 '-N-酰胺类似物在体外没有活性，然而，Iox（腙连接的）免疫缀合物对CEA阳性细胞系具有选择性毒性。
Doxorubicin was modified with five different heterobifunctional reagents to produce drug analogs containing 3'-N- amide or C-13 hydrazone linkage with maleimide. Synthesis and characterization of two new reagents, 4-maleimido-benzohydrazide trifluoroacetate salt (13) and N-(4-maleimidobenzoyl)-6-aminocaprohydrazide trifluoroacetate salt (14) are described here. All Dox maleimido derivatives were conjugated to thiolated anti-carcinoembryonic antigen monoclonal antibody, 11-285-14, via a Michael addition reaction. Antibody-directed cytotoxicity was demonstrated with the MTT assay using combinations of antigen-positive and antigen-negative cell lines. The immunoconjugates prepared from Dox. 3'-N-amide analogs are not active in vitro, however, I)ox(hydrazone-linked) immunoconjugates are selectively toxic to the CEA positive cell line.