The broad long term goal of this research is to develop a new mass spectrometric method for the structural elucidation of oligosaccharides. Oligosaccharides (OS) play a central role in mammalian biology in many fundamental processes such as cell-cell recognition, adhesiveness, control of cell division, cellular differentiation and malignant transformation. Hence, in the study of cancer and other related diseases, a general, sensitive, and accurate method of analysis is clearly desired. Mass spectrometry has the potential to offer many of these features. Our immediate goal is to understand the production and unimolecular chemistry of complex gas-phase oligosaccharide ions. The newly developed external source Fourier transform mass spectrometry instrument will be utilized and further developed for the specific analysis of these compounds. This method is unique and allows ions to be produced and trapped for long periods of time. The addition of the external source has allowed the use of fast atom bombardment to generate gas-phase bio-organic ions. Preliminary experiments have been performed showing major differences between this technique and other mass spectrometric methods. We find that matrix interference in the spectra is minimal add substantial fragmentation is obtained. This is due to the relatively longer detection time scale of the instrument. During the detection period, slow metastable decay occurs and allows oligosaccharide ions to undergo fragmentation. Matrix cluster ions also undergo metastable decomposition. However, these ions fragment more quickly due to the loose nature of the bonding. The result is a spectrum of oligosaccharide ions in the near absence of matrix interference. Studies are proposed to gain a better understanding of the unimolecular decay. In addition, conditions will be obtained to optimize structural information from FAB/FTMS alone (i.e. without further tandem MS determinations). This would make powerful the coupling of liquid chromatography techniques such as flow FAB (and electrospray) to this mass spectral method to analyze complex oligosaccharide mixtures. Direct application to glycolipids and high-mannose compounds will be performed through a collaboration with a natural products chemist and an oligosaccharide biochemists.
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