Fast atom bombardment mass degradation

S. Murao, K.Tanaka, and I. Nojima, Primary structure of paim I, an alpha-amylase inhibitor from Streptomyces corchorushii, determined by the combination of Edman degradation and fast atom bombardment mass spectrometry, Biochemistry 26 (1987), 6483-6488. 

Because of the complexity of the polyether antibiotics little progress has been made in structure determination by the chemical degradation route. X-ray methods were the techniques most successfully applied for the early structure elucidations. Monensin, X206, lasalocid, lysocellin, and salinomycin were included in nineteen distinct polyether x-ray analyses reported in 1983 (190). Use of mass spectrometry (191), and 1H (192) and 13C nmr (141) are also reviewed. More recently, innovative developments in these latter techniques have resulted in increased applications for structure determinations. For example, heteronuclear multiple bond connectivity (hmbc) and homonudear Hartmann-Hahn spectroscopy were used to solve the structure of portimicin (14) (193). Fast atom bombardment mass spectrometry was used in solving the structures of maduramicin alpha and co-factors (58). 

Some discussion on the use of mass spectrometry for end group deteniiination can be found in recent texts."Traditionally mass speclromelric lechniques have required polymers of relatively low molecular weight. Meisters et a/." reported that fast atom bombardment mass spectrometry (FAB-MS) can be applied in the analysis of MM A oligomers to at least hexadecamer. For polymers that degrade by unzipping, pyrolysis GCMS has provided extremely useful data on initiation processes. Thus, Farina et <7/. and Ohtani et described the... 

Ballistreri, A., Garozzo, D., Giuffrida, M., Montaudo, G., Microstructure of Bacterial Poly(j8-hydroxybut5n ate-co-j8-hydrox3rvalerate) by Fast Atom Bombardment Mass Spectrometry. Analysis of their Partial Degradation Products in Novel Biodegradable Microbial Polymers, E.A. Dawes (ed), Kluwer, 1990, pp. 49-64. 

Bradley, C. V., D. H. Williams, and M. R. Hanley Peptide Sequencing Using the Combination of Edman Degradation, Carboxypeptidase Digestion and Fast Atom Bombardment Mass Spectrometry. Biochem. Biophys. Res. Comm. 104, 1223 (1982). Williams, D. H., S. Santikarn, P. B. Oelrichs, F. de Angelis, J. K. Macleod, and R. J. Smith The Structure of a Toxic Octapeptide, Containing 4 D-amino acids, from the Larvae of a Sawfly. Lophyrotoma Interrupta. J. Chem. Soc. (London), Chem. Commun. 1982, 1394. 

To achieve sufficient vapor pressure for El and Cl, a nonvolatile liquid will have to be heated strongly, but this heating may lead to its thermal degradation. If thermal instability is a problem, then inlet/ionization systems need to be considered, since these do not require prevolatilization of the sample before mass spectrometric analysis. This problem has led to the development of inlet/ionization systems that can operate at atmospheric pressure and ambient temperatures. Successive developments have led to the introduction of techniques such as fast-atom bombardment (FAB), fast-ion bombardment (FIB), dynamic FAB, thermospray, plasmaspray, electrospray, and APCI. Only the last two techniques are in common use. Further aspects of liquids in their role as solvents for samples are considered below. 

Physical Chemical Characterization. Thiamine, its derivatives, and its degradation products have been fully characterized by spectroscopic methods (9,10). The ultraviolet spectmm of thiamine shows pH-dependent maxima (11). H, and nuclear magnetic resonance spectra show protonation occurs at the 1-nitrogen, and not the 4-amino position (12—14). The H spectmm in D2O shows no resonance for the thiazole 2-hydrogen, as this is acidic and readily exchanged via formation of the thiazole yUd (13) an important intermediate in the biochemical functions of thiamine. Recent work has revised the piC values for the two ionization reactions to 4.8 and 18 respectively (9,10,15). The mass spectmm of thiamine hydrochloride shows no molecular ion under standard electron impact ionization conditions, but fast atom bombardment and chemical ionization allow observation of both an intense peak for the patent cation and its major fragmentation ion, the pyrimidinylmethyl cation (16). 

Caliceti P, Veronese FM, Marsilio F, Lora S, Seraglia R, and Traldi P. Fast atom bombardment in the structural identification of intermediates in the hydrolytic degradation of polyphosphazenes. Org Mass Spectrom, 1992, 27, 1199-1202. 

Ionization Methods/Processes. The recent development of several new ionization methods in mass spectrometry has significantly improved the capability for the analysis of nonvolatile and thermally labile molecules [18-23]. Several of these methods (e.g., field desorption (FD), Californiun-252 plasma desorption (PD), fast heavy ion induced desorption (FHIID), laser-desorption (LD), SIMS, and fast atom bombardment (FAB) or liquid SIMS) desorb and ionize molecules directly from the solid state, thereby reducing the chance of thermal degradation. Although these methods employ fundamentally different excitation sources, similarities in their mass spectra, such as, the appearance of protonated, deprotonated, and/or cationized molecular ions, suggest a related ionization process. 

Polypeptides of up to approximately 25 residues can be sequenced by the technique of mass spectrometry (MS), which involves an ionization technique called fast atom bombardment (FAB) in concert with a tandem mass spectrometer (two mass spectrometers coupled in series). The sequence of the polypeptide can be obtained from the molecular masses of the various fragments produced in the ionization stage in only a few minutes compared to the hour required for just one cycle of Edman degradation. In addition, mass spectrometry can be used to sequence several polypeptides in a mixture, alleviating the need to completely... 

Early in the history of mass spectrometry (MS), large biomolecules were not analyzed because efficient methods to transport these molecules into the gas phase were unknown. Degradation typically occurred during vaporization of these nonvolatile molecules so that electron ionization of the intact molecular ion was not possible. Ionization by fast atom bombardment (FAB), field desorption (FD), secondary ionization mass spectrometry (SIMS), and plasma desorption (PD)" from the radioactive decay of Cf finally made the ionization and analysis of peptides possible. These latter techniques, although still used today, are not as popular as electrospray... 

Modem mass spectrometric methods greatly help to speed up degradation studies by identifying the molecular mass of peptide fragments. Various desorption techniques, which produce protonated protein ions in the gas phase, are applied. Prominent examples are fast-atom bombardment (FAB) and matrix- assisted laser desorption/ionization (MALDI). Most commonly these techniques provide only the mass of the molecular ion, but they can be coupled with a collision-induced dissociation (CID) procedure. The ions are activated by collisions with neutral target gases, and the peptides dissociate in the gas phase. The resulting mass spectra... 

Because of the low volatility of polymeric materials, many mass spectral methods for polymers have involved pyrolysis (or thermal degradation), and this topic is covered in Chapter 3 (pyrolysis-GC/MS), Chapter 5 (direct pyrolysis-MS), and Chapter 6 (pyrolysis-FI/FD-MS). Chemical degradation methods are discussed in connection with fast atom bombardment analysis (Chapter 7). 

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