THE SIR SUPPLIED DR. THOMAS WITH 20G U-15N AS1 CELLS & 20G UNLABELED ASI CELLS. THE CENTRAL OBJECTIVE OF OUR RESEARCH PROGRAM IS TO DETERMINE THE CONFORMATIONS AND INTERACTIONS OF NUCLEIC ACIDS AND NUCLEOTIDE ANALOGS IN BIOLOGICAL MACROMOLECULAR ASSEMBLIES. THIS OBJECTIVE IS PURSUED PRIMARILY BY METHODS OF RAMAN AND INFRARED VIBRATIONAL SPECTROSCOPY.
OUR SPECIFIC AIMS I NCLUDE THE FOLLOWING: (1) ESTABLISH RAMAN AND INFRARED SPECTRA/STRUCTURE CORRELATIONS TO FACILITATE DNA AND RNA STRUCTURE DETERMINATIONS IN BIOLOGICAL ASSEMBLIES. (2) ESTABLISH RELIABLE QUALITATIVE AND QUANTITATIVE UNDERSTANDING OF CONFORMATION-SENSITIVE VIBRATIONAL MODES OF THE DNA NUCLEOTIDE RESIDUES THROUGH THE COMBINED USE OF NORMAL MODE ANALYSIS AND EXPERIMENTAL DATA FROM LABELED NUCLEOTIDE DERIVATIVES (15N, 13C, 2H AND 18O ISOTOPOMERS). (3) TEST THE DERIVED MOLECULAR FORCE FIELDS BY SYSTEMATIC INVESTIGATION OF MODEL SYSTEMS OF KNOWN THREE- DIMENSIONAL STRUCTURE, AS DETERMINED BY X-RAY CRYSTALLOGRAPHY. (4) APPLY THE METHODS TO NATIVE NUCLEIC ACIDS IN VIRUSES AND GENE REGULATORY COMPLEXES, AND TO SOLUTION STATES OF DNA AND RNA WHICH ARE NOT AMENABLE TO INVESTIGATION BY ALTERNATIVE STRUCTURAL METHODS. THE PROPOSED RESEARCH IS DESIGNED TO IMPROVE OUR UNDERSTANDING OF THE DETAILED CHANGES IN MOLECULAR GEOMETRY WHICH ARE RESPONSIBLE FOR CONFORMATIONAL DEPENDENCE OF RAMAN AND INFRARED BANDS OF DNA AND RNA. THE RESULTS SHOULD PROVIDE A RELIABLE BASIS FOR INTERPRETING VIBRATIONAL SPECTRA OF THE NUCLEIC ACIDS IN TERMS OF LOCAL STRUCTURE (BOND LENGTHS, ANGLES AND TORSIONS) OF THE SUGAR-PHOSPHATE BACKBONE. THE METHODOLOGY WILL BE USEFUL FOR PROBING SENSITIVELY THE STRUCTURE OF DNA IN CONDENSED CHROMOSOMAL STATES AND FOR IDENTIFYING THE LOCUS AND NATURE OF CHANGES IN DNA STRUCTURE WHICH ACCOMPANY PROTEIN BINDING. OUR PREVIOUS WORK IN THIS FIELD IS SUMMARIZED IN RECENT REVIEW ARTICLES (THOMAS & WANG, 1988; THOMAS & TSUBOI, 1993) AND REFERENCES CITED THEREIN.
| Martinez, Rodolfo A; Glass, David R; Ortiz, Erick G et al. (2014) Synthesis of isotopically labeled 1,3-dithiane. J Labelled Comp Radiopharm 57:338-41 |
| Martinez, Rodolfo A; Glass, David R; Ortiz, Erick G et al. (2013) Large-scale preparation of (13) C-labeled 2-(phenylthio)acetic acid and the corresponding labeled sulfoxides and sulfones. J Labelled Comp Radiopharm 56:31-5 |
| Jenkins, Janelle E; Creager, Melinda S; Lewis, Randolph V et al. (2010) Quantitative Correlation between the protein primary sequences and secondary structures in spider dragline silks. Biomacromolecules 11:192-200 |
| Creager, Melinda S; Jenkins, Janelle E; Thagard-Yeaman, Leigh A et al. (2010) Solid-state NMR comparison of various spiders' dragline silk fiber. Biomacromolecules 11:2039-43 |
| Kim, Sun Hee; Aznar, Constantino; Brynda, Marcin et al. (2004) An EPR, ESEEM, structural NMR, and DFT study of a synthetic model for the covalently ring-linked tyrosine-histidine structure in the heme-copper oxidases. J Am Chem Soc 126:2328-38 |
| Ollivault-Shiflett, Morgane; Kimball, David B; Silks, L A Pete (2004) Synthesis of chiral 13C,77Se-labeled selones. J Org Chem 69:5150-2 |
| Schmidt, Bryan; Hillier, Warwick; McCracken, John et al. (2004) The use of stable isotopes and spectroscopy to investigate the energy transducing function of cytochrome c oxidase. Biochim Biophys Acta 1655:248-55 |
| Schmidt, Bryan; McCracken, John; Ferguson-Miller, Shelagh (2003) A discrete water exit pathway in the membrane protein cytochrome c oxidase. Proc Natl Acad Sci U S A 100:15539-42 |
| Gray, Chandele R; Sanz-Cervera, Juan F; Silks, Louis A et al. (2003) Studies on the biosynthesis of asperparaline A: origin of the spirosuccinimde ring system. J Am Chem Soc 125:14692-3 |
| Van Dien, Stephen J; Strovas, Tim; Lidstrom, Mary E (2003) Quantification of central metabolic fluxes in the facultative methylotroph methylobacterium extorquens AM1 using 13C-label tracing and mass spectrometry. Biotechnol Bioeng 84:45-55 |
Showing the most recent 10 out of 72 publications
