Abstract

The proposed project will continue development of the methodology for the determination of detailed molecular structures in non-crystalline environments. Principally, this entails two-dimensional nuclear magnetic resonance techniques analyzed in detail with a complete relaxation matrix analysis and used in conjunction with distance geometry, molecular mechanics and molecular dynamics calculations. Specifically, the methodology will be applied to the investigation of nucleic acid fragments, with an emphasis on those containing adenine (A) or thymine (T). Although related DNA fragments will constitute the majority of studies, analogous RNA and RNA-DNA hybrids will also be subjects for study. Further studies will include modified bases. Finally, binding of drugs which show preference to AT moieties of DNA will be investigated.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM039247-05
Application #
3296050
Study Section
Special Emphasis Panel (SSS (G))
Project Start
1988-02-01
Project End
1993-06-30
Budget Start
1992-02-01
Budget End
1993-06-30
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
Schools of Pharmacy
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Tonelli, Marco; Ulyanov, Nikolai B; Billeci, Todd M et al. (2003) Dynamic NMR structures of [Rp]- and [Sp]-phosphorothioated DNA-RNA hybrids: is flexibility required for RNase H recognition? Biophys J 85:2525-38
Ulyanov, Nikolai B; Bauer, William R; James, Thomas L (2002) High-resolution NMR structure of an AT-rich DNA sequence. J Biomol NMR 22:265-80
Comolli, Luis R; Ulyanov, Nikolai B; Soto, Ana Maria et al. (2002) NMR structure of the 3' stem-loop from human U4 snRNA. Nucleic Acids Res 30:4371-9
Konerding, David; James, Thomas L; Trump, Eric et al. (2002) NMR structure of a gemcitabine-substituted model Okazaki fragment. Biochemistry 41:839-46
Kojima, C; Ulyanov, N B; Kainosho, M et al. (2001) Slow motion in the CAA*TTG sequence of a DNA decamer duplex studied by NMR. Biochemistry 40:7239-46
Song, M; Shao, H; Mujeeb, A et al. (2001) Molten-globule structure and membrane binding of the N-terminal protease-resistant domain (63-193) of the steroidogenic acute regulatory protein (StAR). Biochem J 356:151-8
James, T L (2001) NMR determination of oligonucleotide structure. Curr Protoc Nucleic Acid Chem Chapter 7:Unit 7.2
Tonelli, M; Peters, R J; James, T L et al. (2001) The solution structure of the viral binding domain of Tva, the cellular receptor for subgroup A avian leukosis and sarcoma virus. FEBS Lett 509:161-8
Konerding, D E (2000) The Ensemble/Legacy Chimera extension: standardized user and programmer interface to molecular Ensemble data and Legacy modeling programs. Pac Symp Biocomput :254-65
Filikov, A V; Mohan, V; Vickers, T A et al. (2000) Identification of ligands for RNA targets via structure-based virtual screening: HIV-1 TAR. J Comput Aided Mol Des 14:593-610

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