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Electrospray and MALDI mass spectrometry analysis of biological and pharmaceutical compounds for proteomics and drug discovery

Posted on:2004-03-14Degree:Ph.DType:Dissertation
University:State University of New York at BuffaloCandidate:Bigwarfe, Paul Michael, JrFull Text:PDF
GTID:1451390011454335Subject:Chemistry
Abstract/Summary:
Mass spectrometry has become an invaluable tool to the biological community. It's routine use in both the proteomics and pharmaceutical industries across many scientific disciplines. Electrospray ionization and matrix-assisted laser desorption ionization are the two most common methods by which biological samples are brought into the gas phase. Low-flow electrospray, or nanospray, is employed for the analysis of small sample volumes. Polyaniline-coated nanospray emitters, developed in this laboratory, had their performance measured in the negative ion mode. These emitters were found to ionize a variety of biological samples without the loss of signal due to electrical discharge, as is the case with most commercially available devices. Additionally, it was found that utilizing the negative ion mode in tandem with the positive mode increased the accuracy of protein identification in proteomic analysis. This accuracy improvement held true for MALDI analysis of protein digests as well. Limitations and suggested improvements to proteomic methodologies are also discussed.; The anti-cancer agent paclitaxel was also investigated by electrospray ionization mass spectrometry. Hydrogen/Deuterium exchange experiments were used to prove the existence of a solution-phase dimer of the drug. Paclitaxel's drug target, the protein tubulin, was also studied by ESI-MS. Other examples of biological molecules, including oligonucleotides, that can be analyzed by mass spectrometry are also given. In general, the work in this dissertation illustrates the variety of applications mass spectrometry is useful for in the biological realm.
Keywords/Search Tags:Mass spectrometry, Biological, Electrospray, Drug
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