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.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Special Emphasis Panel (ZRG1-BMT (01))
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Edmonds, Charles G
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Indiana University Bloomington
Schools of Arts and Sciences
United States
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Hilderbrand, Amy E; Myung, Sunnie; Clemmer, David E (2006) Exploring crown ethers as shift reagents for ion mobility spectrometry. Anal Chem 78:6792-800
Hilderbrand, Amy E; Clemmer, David E (2005) Determination of sequence-specific intrinsic size parameters from cross sections for 162 tripeptides. J Phys Chem B 109:11802-9
Valentine, Stephen J; Liu, Xiaoyun; Plasencia, Manolo D et al. (2005) Developing liquid chromatography ion mobility mass spectometry techniques. Expert Rev Proteomics 2:553-65
Taraszka, John A; Gao, Xinfeng; Valentine, Stephen J et al. (2005) Proteome profiling for assessing diversity: analysis of individual heads of Drosophila melanogaster using LC-ion mobility-MS. J Proteome Res 4:1238-47
Koeniger, Stormy L; Valentine, Stephen J; Myung, Sunnie et al. (2005) Development of field modulation in a split-field drift tube for high-throughput multidimensional separations. J Proteome Res 4:25-35
Taraszka, John A; Kurulugama, Ruwan; Sowell, Rena A et al. (2005) Mapping the proteome of Drosophila melanogaster: analysis of embryos and adult heads by LC-IMS-MS methods. J Proteome Res 4:1223-37
Sowell, Rena A; Koeniger, Stormy L; Valentine, Stephen J et al. (2004) Nanoflow LC/IMS-MS and LC/IMS-CID/MS of protein mixtures. J Am Soc Mass Spectrom 15:1341-53
Valentine, Stephen J; Koeniger, Stormy L; Clemmer, David E (2003) A split-field drift tube for separation and efficient fragmentation of biomolecular ions. Anal Chem 75:6202-8
Hilderbrand, Amy E; Myung, Sunnie; Barnes, Catherine A Srebalus et al. (2003) Development of LC-IMS-CID-TOFMS techniques: analysis of a 256 component tetrapeptide combinatorial library. J Am Soc Mass Spectrom 14:1424-36
Myung, Sunnie; Lee, Young Jin; Moon, Myeong Hee et al. (2003) Development of high-sensitivity ion trap ion mobility spectrometry time-of-flight techniques: a high-throughput nano-LC-IMS-TOF separation of peptides arising from a Drosophila protein extract. Anal Chem 75:5137-45

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