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

一种识别生物活性食品成分分子靶点的新方法

• 批准号: 8020054
• 负责人: JING HUANG
• 金额: $ 16.25万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-03 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8020054
• 关键词: Affinity; Aging; Binding; Biochemical; Biological; Blueberries; Cancer Cell Growth; Cells; Chemicals; Chocolate; Communities; Complex Mixtures; Data; Development; Diet; Drug Interactions; Drug usage; Food; General Population; Goals; Green tea; Human; Immobilization; Intervention; Knowledge; Light; Malignant Neoplasms; Methods; Modification; Molecular Target; Operative Surgical Procedures; Pathway interactions; Pharmaceutical Preparations; Plants; Prevention; Preventive; Proteins; Proteolysis; Protocols documentation; Radiation therapy; Structure; Synthesis Chemistry; Techniques; base; bioactive food component; cancer prevention; chemical genetics; chemotherapy; diet and cancer; gallocatechol; information gathering; interest; novel; public health relevance; research study; small molecule; success; web interface

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.

描述（由申请人提供）：预防癌症的生物活性食品化合物已有详细记录。清楚地了解这些食物成分的分子靶点对于制定有效的抗癌饮食策略至关重要。尽管已经发展了许多方法，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点识别仍然是一个尚未解决的挑战。目前基于亲和力的靶点识别技术受到单独修改每种药物的必要性的限制，而间接的、非亲和力的方法则依赖于药物诱导特定生化或细胞读数的能力。该项目提出了一种新颖的、普遍适用的靶点识别方法（DARTS），该方法可以分析小分子与其蛋白质靶点的直接结合，而无需对小分子进行修饰或固定。具体目标是 1) 建立强大的 DARTS 协议，用于识别生物活性食品成分的分子靶标，2) 使用 DARTS 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，这些研究将对我们对饮食与癌症之间联系的理解产生重大影响，并揭示癌症预防和衰老干预的新机制和目标。 公共卫生相关性：我们的食品中含有癌症预防剂，这是有据可查的。清楚地了解这些生物活性食品成分的分子靶标具有挑战性，但对于制定有效的抗癌饮食策略至关重要。该项目开发了一种新颖且通用的方法来识别抗癌食品成分的分子靶点。