SBIR Phase I: High-Throughput Purification of Combinatorial Libraries

SBIR 第一阶段：组合文库的高通量纯化

• 批准号: 0128691
• 负责人: Jack Syage
• 金额: $ 9.99万
• 依托单位: SYAGEN TECHNOLOGY INC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0128691&HistoricalAwards=false
• 关键词: SBIR; Phase; Throughput; Purification; Combinatorial

This Small Business Innovation Research (SBIR)Phase I project will develop a highly-parallel, mass-selected purification system for large pharmaceutical drug libraries. The need for high-throughput purification is driven by the industry recognition that combinatorial chemistry samples must still be purified even after chemical screening. This is a daunting task considering the exponentially increasing number of drug candidates being synthesized by combinatorial and parallel methods. This proposal will examine monolithic parallel flash chromatography and preparative liquid chromatography configurations. The key enabling technology is photoionization mass spectrometry, which permits accurate molecular detection in mixtures of compounds without the problems of competition-for-charge and ion suppressions that plague conventional ionization methods. This will make it possible to monitor several chromatography columns at the same time. The goal of the project is to have a purification system in place that has a practical purification rate of 1 min per sample (16 parallel purifications in about 16 min) corresponding to a potential 16 hr daily rate of 960 sample purifications per day. The commercial application of this project will be in the important niche market of molecular analysis and screening for drug discovery.

这个小型企业创新研究(SBIR)第一阶段项目将为大型药物库开发一个高度并行的、大规模选择的纯化系统。对高通量纯化的需求是由于行业认识到，即使在化学筛选之后，组合化学样品仍然必须进行纯化。考虑到通过组合和并行方法合成的候选药物的数量呈指数级增长，这是一项艰巨的任务。本提案将考察整体平行闪光层析和制备液相色谱构型。关键的使能技术是光电离质谱，它允许在化合物混合物中进行准确的分子检测，而不会出现困扰传统电离方法的电荷竞争和离子抑制问题。这将使同时监测多个色谱柱成为可能。该项目的目标是建立一个净化系统，每个样品的实际净化速度为1分钟(16次并行净化约16分钟)，相当于潜在的每天16小时的960次样品净化。该项目的商业应用将在药物发现的分子分析和筛选这一重要的利基市场。