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).

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biomedical Research Support Shared Instrumentation Grants (S10)
Project #
1S10RR006287-01
Application #
3520986
Study Section
Special Emphasis Panel (SSS (A))
Project Start
1991-05-22
Project End
1992-05-21
Budget Start
1991-05-22
Budget End
1992-05-21
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Public Health
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115