GAS PHASE ION SEPARATIONS FOR COMB LIBRARY ANALYSIS

用于梳库分析的气相离子分离

• 批准号: 6041391
• 负责人: DAVID E. CLEMMER
• 金额: $ 27.77万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6041391
• 关键词: analytical method; biomedical equipment development; chemical models; combinatorial chemistry; electrospray ionization mass spectrometry; gas; ions; mass spectrometry; oligonucleotides; organic chemicals; peptide library; physical separation; physical state

This proposal describes a program for developing gas-phase ion separation strategies for the analysis of complex biomolecular mixtures such as combinatorial libraries. Preliminary data show that a new ion mobility/time-of-flight mass spectrometry technique combined with electrospray ionization allows components of complex peptide mixtures to be simultaneously characterized. Th this approach the components of the mixture are ionized and the ions are separated by differences in their mobilities through an inert buffer gas before being dispersed into a mass spectrometer. The gas-phase separation step allows structural and sequence isomers to be distinguished. An important feature of the proposal is the development of instrumentation that is capable of parallel sequencing of multiple mobility-separated components of a mixture. This is feasible because fragment ions will be formed after mobility separation and thus are labeled according to parent ion mobilities. Applications of the proposed techniques to several types of libraries (peptide, oligonucleotide, and organic molecule) are outlined. The ability to characterize isomers within a given m/z ratio will have a tremendous impact on the utility of mass spectrometric methods in revealing whether or not expected library components are truly present. This will be a powerful tool in refinement of synthetic methods, and will provide opportunities for development of new search strategies.

这项建议描述了一项计划，用于开发气相离子分离策略，用于分析复杂的生物分子混合物，如组合文库。初步数据显示，一种新的离子迁移率/飞行时间质谱学技术与电喷雾电离相结合，可以同时表征复杂多肽混合物的组成。在这种方法中，混合物的组成被电离，离子通过惰性缓冲气体的迁移率差异而分离，然后被分散到质谱仪中。气相分离步骤允许区分结构和序列异构体。该提案的一个重要特点是开发了能够对混合物的多个流动性分离的组分进行并行排序的仪器。这是可行的，因为碎片离子将在迁移率分离后形成，从而根据母离子的迁移率进行标记。概述了所提出的技术在几种类型的文库(多肽、寡核苷酸和有机分子)中的应用。在给定的m/z比范围内表征同分异构体的能力将对质谱学方法在揭示预期的文库成分是否真正存在方面的应用产生巨大的影响。这将是改进合成方法的有力工具，并将为开发新的搜索策略提供机会。