A state-of-the-art multi-nuclear NMR instrument operating at a magnetic field of 11.8 Tesla is needed for a group of 8 major and 19 minor users. Of the major users, Dr. Aisen proposes proton NMR studies of procine uteroferrin, with the hope of relating metal-ligand interactions at the active site to the biochemical activity of the protein. Dr. Peisach will use NMR in his studies of hemoproteins to determine the structure of the prosthetic group in sulfhemoglobin and sulfmyoglobin. Dr. Atkinson used NMR for comparative structural analyses of N-linked complex carbohydrates in glycoproteins from surface and intracellular membranes of animal cells and viruses. Dr. Stanley is engaged in investigations of glycosylation defects exhibited by Chinese hamster ovary cell mutants shown to possess structural alterations in carbohydrates at the cell surface. Proton NMR is used to obtain the complete sugar composition, the linkage specificities and partial or complete sequence of sugars from 25-50 nmole of a purified glycopeptide. Structurally characterized carbohydrates are used to search for specific enzyme lesions which might provide the basis of each mutant genotype. Dr. Brewer will continue his studies of the interactions of simple and complex carbohydrates with Concanavalin A and will extend them to lentil and pea lectins to obtain insights into the saccharide binding activities of the lectins and their interactions with cell membranes. Dr. Cowburn's research is aimed at characterizing the conformational features of insulin and relaxin required for bioactivity, using detailed conformational analyses, by proton NMR, of native hormones, and their active and inactive analogs. Dr. Fabry is studying interactions of abnormal hemoglobins with the cellular constituents using abnormal red cells whose heterogeneity has been resolved by isopycnic centrifugation. She also uses NMR to study the products and mechanism of reaction of glucose-6P and glucose (found elevated in red cells in diabetes) and acetaldehyde (found elevated in red cells in alcoholism) with hemoglobin. Dr. Gupta proposes NMR studies of a variety of cells and tissues. He seeks to understand possible regulatory roles of metal ions in cellular proliferation, differentiation, volume regulation, and hormonal control of various cellular processes, to understand how the concentrations of intracellular ions are managed by membrane transport processes, and how such regulation goes astray in disorders such as cancer, hypertension, diabetes, and sickle cell disease.
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