The field of mass spectrometry has developed dramatically in the past few years. Major advances have been made in capillary gas chromatographic-accurate mass mass spectrometry; new ionization techniques such as fast atom bombardment; extended mass range (Greater 1000 daltons) instruments; tandem mass spectrometry (MS/MS); and computer data acquisition and processing. It is now possible to attempt mass spectrometric analysis of important large biological molecules, such as peptide and carbohydrate oligomers.
The aim of this proposal is to apply and further develop new techniques in mass spectrometry to solve specific problems in the chemical analysis of peptide and carbohydrate oligomers. Unmodified and modified peptide oligomers will be obtained from: cytolytic peptides and proteins (melittin; Delta-hemolysin; human eosinophil major basic protein); a calcium dependent bioluminescent protein (aequorin); calcium binding proteins; opiate-binding peptides; cholecystokinin peptides; vitamin K-dependent protein factors; and the cyclic undecapeptide drug cyclosporine. Oligosaccharides analyzed will be of the high mannose type isolated from the urine of patients with mannosidosis; trehalose-containing lipooligosaccharide mycobacterial antigens; and heparin fragments generated by heparinase. Significance: First, significant contributions will be made to the structural and sequence analysis of a number of important biological peptide and saccharide oligomers. Second, the unique applications of new techniques in mass spectrometry to the solutions of these specific problems will be demonstrated. A significant contribution will therefore be made to further the development of new mass spectrometric techniques for the analysis of significant biological oligomers.
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