一种新型的紫杉烷生物素共轭物的制备

生物素与肿瘤细胞表面的生物素受体结合,通过受体介导的内吞作用将共轭物摄入细胞内,二硫键在肿瘤细胞中能够开链,释放出活性物质,实现靶向性给药,从而大大降低传统化疗药物因缺乏对肿瘤细胞的选择性而引起的毒副作用。用巯基置换的方式,合成含有二硫键的连接链;用将羧酸基团转化为酰肼基团的方法,将生物素转化为生物素酰肼;选用具有抗多药耐药性的含氟紫杉烷SB-T-12854作为细胞毒分子;通过含有二硫键的连接链将含氟紫杉烷化合物SB-T-12854与生物素酰肼进行偶连,形成一种新型的紫杉烷生物素共轭物。

Synthesis of novel taxoid-biotin conjugate

The conjugate is designed to be specific to the biotin receptors overexpressed on tumor cell surface and internalized efficiently through receptor-mediated endocytosis, followed by smooth drug release via glutathione-triggered self-immolation of the linker. An efficient mechanism-based tumor-targeting drug delivery system, based on tumor-specific biotin-receptor mediated endocytosis, has reduced the undesirable side effects associated with the traditional cytotoxic chemotherapeutic agents which lack of selectivity to tumor cells and normal cells. The disulfide linker is prepared by subsititution of sulfhydryl group. The tumor-targeting molecule biotin moiety is prepared by conversion of carboxylic acid group to acyl hydrazide group. Fluorotaxane SB-T-12854 with anti multidrug resistance is choosed as th cytotoxic agent. The tumor-targeting drug delivery system is a novel conjugate of a cytotoxic agent (SB-T-12854), a disulfide linker and a tumor-targeting molecule (biotin).