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C1027是链霉菌株产生的大分子肽类新抗癌抗生素,对肿瘤细胞具有显著的杀伤作用,它由一条肽链和一个发色团组成,后者是主要活性部分。本研究用甲醇拆分C1027并重新组建,重建的C1027与天然C1027活性相似;C1027的重建是特异的,肽链与发色团的结合不受BSA竟争影响。肽链不能与表阿霉素组建;单抗H16(IgG_1)不能与发色团组建。我们用不同的方法分别制备了C1027与抗人肝癌单抗H16直接偶联物和组装偶联物(单抗与肽链连接后再加入发色团);克隆形成测定,前者IC_(50)为42pmol·L~(-1),后者为5.5pmol·L~(-1);C1027与无关抗体M3组装偶联物的IC_(50)为240pmol·L~(-1)。结果表明H16-C1027组装偶联物对肝癌细胞的抑制作用比直接偶联物明显增强,并具有选择性杀伤作用。
C1027 is a macromolecular peptide anti-cancer antibiotic produced by Streptomyces strains, which has a significant killing effect on tumor cells. It consists of a peptide chain and a chromophore, which is the main active part. In this study, C1027 was resolved by methanol and reconstituted. The reconstructed C1027 had similar activity to that of C1027. The reconstitution of C1027 was specific, and the binding of peptide to chromophore was not affected by BSA competition. The peptide chain can not be formed with epirubicin; the monoclonal antibody H16 (IgG_1) can not be formed with the chromophore. We used different methods to prepare C1027 and anti-human liver cancer monoclonal antibody H16 direct conjugate and assembly conjugate (monoclonal antibody and peptide chain and then join the chromophore); clone formation assay, the former IC 50 42 pmol·L ~ (-1), while the latter was 5.5 pmol·L ~ (-1). The IC 50 of the conjugate of C1027 with irrelevant antibody M3 was 240 pmol·L -1. The results showed that the inhibitory effect of the conjugate of H16-C1027 on hepatocellular carcinoma cells was significantly enhanced compared with the direct conjugate, and has a selective killing effect.