Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
J Nat Prod. 2010 Apr 23;73(4):751-4. doi: 10.1021/np9007359.
The development of an automated, high-throughput fractionation procedure to prepare and analyze natural product libraries for drug discovery screening is described. Natural products obtained from plant materials worldwide were extracted and first prefractionated on polyamide solid-phase extraction cartridges to remove polyphenols, followed by high-throughput automated fractionation, drying, weighing, and reformatting for screening and storage. The analysis of fractions with UPLC coupled with MS, PDA, and ELSD detectors provides information that facilitates characterization of compounds in active fractions. Screening of a portion of fractions yielded multiple assay-specific hits in several high-throughput cellular screening assays. This procedure modernizes the traditional natural product fractionation paradigm by seamlessly integrating automation, informatics, and multimodal analytical interrogation capabilities.
描述了一种自动化、高通量的分离程序的开发，用于制备和分析用于药物发现筛选的天然产物文库。从世界各地的植物材料中提取天然产物，首先用聚酰胺固相萃取小柱进行预分离，以去除多酚，然后进行高通量自动化分离、干燥、称重和重新格式化，用于筛选和储存。使用 UPLC 与 MS、PDA 和 ELSD 检测器分析馏分，提供有助于鉴定活性馏分中化合物的信息。对部分馏分的筛选在几种高通量细胞筛选测定中产生了多个特定测定的阳性结果。该方法通过无缝集成自动化、信息学和多模式分析检测能力，使传统的天然产物分离范式现代化。
