A Novel Method for Identifying the Molecular Targets of Bioactive Food Components

描述（由申请人提供）：癌症预防生物活性食品化合物已被充分证明。清楚地了解这些食物成分的分子靶标是制定有效的抗癌饮食策略的基础。尽管发展了许多方法，但由于小分子结构、活性和作用机制的巨大多样性，生物活性化合物的靶标鉴定仍然是一个未满足的挑战。目前基于亲和力的靶标鉴定技术受到单独修改每种药物的必要性的限制，而间接的、非亲和力的方法依赖于药物诱导特定生化或细胞读数的能力。本项目提出了一种新颖的，普遍适用的靶标识别方法（DARTS），该方法可以分析直接与蛋白质靶标结合的小分子，而无需对小分子进行修饰或固定化。具体目标是1)建立一个强大的DARTS方案，用于识别生物活性食品成分的分子靶标；2)使用DARTS来确定生物活性食品化合物的分子靶标，以解释其对人类癌细胞生长的抑制作用。如果成功，这些研究将对我们理解饮食与癌症之间的联系产生重大影响，并为癌症预防和衰老干预提供新的机制和目标。

DESCRIPTION (provided by applicant): Cancer preventive bioactive food compounds are well documented. A clear understanding of the molecular targets for these food components is fundamental to the development of effective diet strategies against cancer. Despite the development of many methods, target identification for bioactive compounds is an unmet challenge due to the huge diversity in small-molecule structure, activity, and mechanisms of action. Current affinity-based target identification techniques are limited by the necessity to modify each drug individually, while indirect, non-affinity based approaches are dependent on the drug's ability to induce specific biochemical or cellular readouts. This project presents a novel, universally applicable target identification approach (DARTS) that analyzes direct small-molecule binding to its protein target without requiring modification or immobilization of the small molecule. The specific aims are to 1) establish a robust DARTS protocol for identifying the molecular targets of bioactive food components, and 2) to use DARTS to determine the molecular targets of bioactive food compounds that explain their inhibition of human cancer cell growth. If successful, the studies will have a major impact on our understanding of the linkage between diet and cancer, and shed light on new mechanisms and targets for cancer prevention and aging intervention. PUBLIC HEALTH RELEVANCE: Cancer preventive agents in our food are well documented. A clear understanding of the molecular targets for these bioactive food components is challenging but fundamental to the development of effective diet strategies against cancer. This project develops a novel and universal method to identify the molecular targets for anti-cancer food components.