GC/SFC -MS INSTRUMENT : TRIPLE QUADRUPOLE

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This application; (i) describes ongoing research of several collaborating groups that depend on, a detailed structural analysis of oligosaccharide, glycolipid, and glycoprotein samples; (ii) outlines two new AIDS projects funded to study the structure-function relationships of the HIV & T-Cell binding glycoproteins; (iii) summarizes oligosaccharide sequencing methodology that is expanding requests for collaboration and instrument time; and, juxtaposed to the greater need, (iv) discusses the constraints imposed by outmoded instrumentation. Recent published reports (1-7) document past collaborations and these ongoing efforts require access to more contemporary instrumentation and recently developed methodology (8- 10). The latter techniques combine: (a) improved component resolution and molecular wight identification by SFC-MS; (b) enhanced glycan detection by conjugation with an NCI-sensitive adduct; and, (c) linkage and branching information by periodate oxidation, aldehyde derivatization and SFC-MS. Application of these techniques require negative ion focusing, fast scanning, SFC-MS, and higher mass analysis; capabilities not available with our 1978 vintage MAT 312. The proposed triple quadrupole would; (i) diffuse many problems from the ZAB, freeing time more appropriate to that instrument, (e.g., high resolution, high energy CID, MIKES, linked scan analysis, high mass transmission); (ii) serve as a more routine instrument for biopolymer sequencing by SFC-MS and microbore HPLC-MS; (iii) sustain GC-MS capability over the next decade as we phase out the MAT-312; and, (iv) provide an opportunity to further develop SFC-MS methodology for glycan structure by studying low energy collisions, ion confinement, and related techniques that may yield greater structural detail on focused ions. In addition to in-house research, and the user-groups identified, this facility serves the Medical Area as a resource for routine sample analysis, and as a training resource for visiting scientists, postdoctoral fellows, and graduate students in the expanding areas of glycoconjugate chemistry, biochemistry, and applied mass spectrometry. (Ref. 1010, see Appendix).