Paclitaxel Carrier from Protein Library

本项目的长期目标是制备一种可用于药物的蛋白质药物载体 靶向于实体肿瘤。大分子被证明聚集在周围的渗漏血管中， 快速生长的肿瘤组织然而，这些分子从它们被保留的地方移动到 由于肿瘤部位周围的不利对流或溶剂阻力，实际肿瘤细胞的生长非常缓慢。在 相反，小分子（<10 kDa）可以利用浓度梯度决定的扩散进入位点 的行动。本研究的总体目标是：（1）合成水溶性生物素衍生物 （2）通过mRNA展示系统鉴定高亲和力紫杉醇结合蛋白，（3）进一步 选择那些当pH值降低到6.5或温度升高到42 ℃时会释放紫杉醇的药物，（4） 将这些蛋白质共价偶联到树枝状聚合物上以增加总MW，以及（5）最终表征 在紫杉醇结合和释放方面组装。

The long term objective of this project is to prepare a protein-based drug carrier that can be used in drug targeting to solid tumors. Macromolecules are shown to accumulate in leaky blood vessels surrounding rapidly growing tumor tissue. However, the movement of these molecules from where they are retained to actual tumor cells is extremely slow, due to unfavorable convection, or solvent drag, around the tumor site. In contrast, small molecules (<10 kDa)can utilize diffusion dictated by concentration gradient to access the site of action. The overall goals of the proposed study are to: (1) synthesize water-soluble biotinylated derivative of paclitaxel, (2) identify high-affinity paclitaxel-binding proteins via the mRNA display system, (3) further select those that will release paclitaxel when pH is lowered to 6.5 or temperature is elevated to 42¿C, (4) covalently couple these proteins to a dendrimer to increase the overall MW, and (5) finally characterize the assembly in terms of paclitaxel binding and release.