论文部分内容阅读
在肝癌单克隆抗体Ｈｅｐａｍａ－１－人血清白蛋白－ＭＴＸ结合物的制备中，首先ＭＴＸ在二环己基碳二亚胺（Ｄｉｃｙｃｌｏｈｅｘｙｌｃａｒｂｏｄｉｍｉｄｅ，ＤＣＣ）作用下，与Ｎ－羟基琥珀酰亚胺（Ｎ－Ｈｙｄｒｏｘｙｓｕｃｃｉｎｉｍｉｄｅ，ＮＨＳ）反应，得到ＭＴＸ活性酯，中间载体ＨＳＡ与ＳＰＤＰ作用引入巯基，再与ＭＴＸ活性酯反应得到ＨＳ－ＨＳＡ－ＭＴＸ。然后与碘乙酰化单克隆抗体Ｈｅｐａｍａ－Ｉ反应，获得硫醚键连接的交联物。交联物中Ｈｅｐａｍａ－Ｉ：ＨＳＡ：ＭＴＸ克分子比为１１．６３０，对靶细胞ＢＥＬ－７４０５及对照细胞ＨｅＬａ的杀伤效率，以交联物按ＭＴＸ的克分子浓度计算，ＩＣ５０（５０％抑止率）分别为２．５×１０－８ｍｏｌ／Ｌ和６．４×１０－７ｍｏｌ／Ｌ。单独ＭＴＸ对上述二种细胞株不显示选择性杀伤，ＩＣ５０均为７．１×１０－８ｍｏｌ／Ｌ。
In the preparation of hepatocarcinoma monoclonal antibody Hepama-1-human serum albumin-MTX conjugate, first MTX is treated with dicyclohexylcarbodiimide (DCC) and N-hydroxysuccinimide (N- Hydroxysuccinimide (NHS) reaction gives MTX active ester, intermediate carrier HSA interacts with SPDP to introduce mercapto group, and reacts with MTX active ester to obtain HS-HSA-MTX. It was then reacted with iodoacetylated monoclonal antibody Hepama-I to obtain thioether-linked crosslinks. The molecular weight ratio of Hepama-I:HSA:MTX in the cross-linked compound was 11.630, and the killing efficiency of the target cell BEL-7405 and the control cell HeLa was calculated as the cross-linked compound in terms of the molar concentration of MTX, IC50 (50% inhibition The rates were 2.5 x 10-8 mol/L and 6.4 x 10-7 mol/L, respectively. MTX alone did not show selective killing on the above two cell lines, and the IC50 was 7.1×10 −8 mol/L.