Adaptations and methodologies for enhanced identification of lead compounds

增强先导化合物鉴定的适应性和方法

• 批准号: 8763547
• 负责人: Kirk Gustafson
• 金额: $ 39.47万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8763547
• 关键词: Biological; Biological Assay; Biological Factors; Chemicals; Circular Dichroism; Collection; Complex; Complex Mixtures; Databases; Effectiveness; Goals; Hydrolysis; Laboratories; Lead; Libraries; Methodology; Methods; Nuclear Magnetic Resonance; Outcome; Porifera; Property; Relative (related person); Resources; Sampling; Solutions; Source; Speed; System; Techniques; liquid chromatography mass spectrometry; novel; programs; repository; screening

A program was implemented to prefractionate a large subset of extracts from the Natural Products Repository. This initiative has generated a substantial collection of prefractionated samples (18,000) that are more suited for the high-throughput natural products discovery efforts our laboratory is engaged in. The extract prefractionation library we constructed provides a high-value screening resource for enhanced lead identification in a variety of different assay systems.We have also focused on expansion of our pure natural products library, since this provides the ideal solution to the problems associated with screening extracts. Methods to enhance our structural elucidation capabilities are another major focus of this project, with a special emphasis on techniques used to assign the relative and absolute configuration of unknown natural products. Some of the challenging stereochemical determinations achieved by the group employed diverse methodologies including hydrolysis, derivatization, and liquid chromatography-mass spectrometry analyses, nuclear magnetic resonance (NMR) database comparisons, and circular dichroism (CD) studies. The complete structural elucidation of a novel sponge-derived phosphomacrolide, utilized a combination of micro-scale chiral derivatization and chemical interconversion, with NMR and CD analyses.

实施了一项程序，以预先从天然产品存储库中提取大量提取物。该计划已产生了大量的预分级样品（18,000），这些样本更适合于高通量的天然产品发现工作，我们的实验室参与了我们构建的提取预拆卸库，可提供高价值的筛选资源，以增强铅识别在各种不同的分析系统中，我们还针对各种不同的筛选了我们的纯天然产品，这是一个理想的自然产品。增强我们的结构阐明能力的方法是该项目的另一个主要重点，特别强调用于分配未知天然产品的相对和绝对配置的技术。该小组实现的一些具有挑战性的立体化学确定采用了多种方法，包括水解，衍生化和液相色谱 - 质谱分析，核磁共振（NMR）数据库比较以及圆形二角主义（CD）研究。新型海绵来源的磷酸果蝇的完整结构阐明利用了微尺度手性衍生物和化学互转换的结合，以及NMR和CD分析。