A 400 MHz NMR spectrometer is requested to meet the needs of an expanding user group principally at the Homewood campus of The Johns Hopkins University from the Departments of Chemistry, Biology and Biophysics. A range of problems of chemical and biological significance is described: (1) bioinorganic modeling of metalloenzyme active sites, containing notably iron and copper, as well as copper-mediated dehalogenation reactions and their role in the environment. (2) studies of site-specific generation of radical intermediates in nucleic acid strand cleavage and of relevance to oxidative stress. (3) development of catalytic, asymmetric processes to synthesize beta-lactams and beta-amino acids and the introduction of fluorine. (4) photoinduced electron-, atom-, and molecule-transfer reactions from inorganic coordination compounds as both tests of theory and applications at nanocrystalline semiconductor interfaces and as occur in Cu(I/II) redox chemistry. (5) development and study of new photochemical precursors of nitric oxide as potential drugs, for example, diazeniumdiolates; and the generation and study of oxynitrenes. (6) preparation and investigation of synthetic analogues of metalloproteins, for example, of peptide deformylase; and the synthesis, characterization and reactivity of aza-substituted corrole macrocycles. (7) instrumental support of biosynthetic and synthetic investigations of aflatoxin and the beta-lactam antibiotics; and the design and synthesis of inhibitors of fatty acid synthase as potential therapeutics in cancer, tuberculosis and obesity. (8) synthesis of vitamin D3 analogues (deltanoids) as chemoprotective and chemotherapeutic agents, and the preparation of trioxanes as simplified structural mimics of artemisinin natural products as potential peroxide anti-malarials. (9) investigation of the hypothesis that aromatic amino acids are required to specify a distinct conformational state by NMR spin relaxation techniques, to elucidate important parameters for protein design.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biomedical Research Support Shared Instrumentation Grants (S10)
Project #
1S10RR017850-01A1
Application #
6735938
Study Section
Special Emphasis Panel (ZRG1-PB (30))
Program Officer
Tingle, Marjorie
Project Start
2004-03-01
Project End
2006-02-28
Budget Start
2004-03-01
Budget End
2006-02-28
Support Year
1
Fiscal Year
2004
Total Cost
$363,713
Indirect Cost
Name
Johns Hopkins University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218