Paclitaxel Carrier from Protein Library

来自蛋白质库的紫杉醇载体

• 批准号: 7064999
• 负责人: Venita Gresham WATSON
• 金额: $ 2.88万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7064999
• 关键词: binding proteins; biodegradable product; biotechnology; calorimetry; chemical synthesis; drug delivery systems; drug discovery /isolation; membrane transport proteins; microdialysis; nanotechnology; neoplasm /cancer chemotherapy; paclitaxel; peptide library; polymerase chain reaction; predoctoral investigator; small molecule; translation factor

DESCRIPTION (provided by applicant): 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.

项目描述（由申请人提供）：该项目的长期目标是制备一种基于蛋白质的药物载体，可用于实体肿瘤的药物靶向。大分子在快速生长的肿瘤组织周围渗漏的血管中积聚。然而，由于肿瘤部位周围不利的对流或溶剂阻力，这些分子从它们保留的地方移动到实际的肿瘤细胞是极其缓慢的。相反，小分子（<10 kDa）可以利用浓度梯度决定的扩散进入作用部位。本研究的总体目标是：(1)合成水溶性生物素化紫杉醇衍生物；(2)通过mRNA展示系统鉴定高亲和的紫杉醇结合蛋白；(3)进一步选择在pH降至6.5或温度升高至42℃时释放紫杉醇的蛋白；(4)将这些蛋白与树状大分子共价偶联以增加总分子量；(5)最终表征紫杉醇结合和释放的组装。