We propose to continue the operation of a national stable isotope resource (SIR) as part of the larger ICONs program at the Los Alamos National Laboratory. The ICONs program, named for the isotopes of carbon (12C, 13C), oxygen (16O, 17O, 18O), and nitrogen (14N, 15N), includes the production of large quantities of separated isotopes by low temperature distillation of CO and NO gases. The principal goal of the SIR is to promote the development of new application of these isotopes to solving fundamental problems in biochemistry, biophysics and practical problems in medical science. The research component of the proposal suggests development of efficient procedures for specific labeling of amino acids, nucleic acids, and enzyme cofactors. By making these materials available to the research community, the Resource will contribute to fundamental studies of protein and nucleic acid structure, protein-nucleic acid interactions, and structure- function relations in heme proteins. The Resource will continue to carry out a spectrum of collaborative and service activities aimed at broadening the uses for stable isotopes in biomedical research, and it will contribute to the developing commerce in stable isotopically labeled compounds by devising efficient procedures for converting labeled CO and NO to useful materials. The particular compounds which become the focus of Resource activities will be selected in consultation with the Resource's Advisory Committee and will be provided to external investigators on a competitive basis. This is one of the most important services of the Resource.
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