Abstract

Natural modifications in nucleic acids, such as those which occur in RNA following transcription, are implicated in a variety of roles in cellular processes, including stabilization of secondary and tertiary structure, modulation of protein- nucleic acid interactions, and adaptation to cellular stress. It is proposed to develop new and improved analytical strategies for structural characterization and sequence placement of modified nucleotides in nucleic acids, based primarily on electrospray ionization and tandem mass spectrometry. Emphasis will be placed on E. coli 16S rRNA as a model system, but elements of the methods proposed are also applicable to structural problems involving DNA, xenobiotically modified nucleic acids and synthetic oligonucleotide analogs.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM021584-26
Application #
6138360
Study Section
Metallobiochemistry Study Section (BMT)
Program Officer
Edmonds, Charles G
Project Start
1978-01-01
Project End
2001-12-31
Budget Start
2000-01-01
Budget End
2001-12-31
Support Year
26
Fiscal Year
2000
Total Cost
$322,596
Indirect Cost

  Institution

Name
University of Utah
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112

  Publications

Rozenski, J; McCloskey, J A (1999) Determination of nearest neighbors in nucleic acids by mass spectrometry. Anal Chem 71:1454-9
Qiu, F; McCloskey, J A (1999) Selective detection of ribose-methylated nucleotides in RNA by a mass spectrometry-based method. Nucleic Acids Res 27:e20
Mitchell, S S; Whitehill, A B; Trapido-Rosenthal, H G et al. (1997) Isolation and characterization of 1,3-dimethylisoguanine from the Bermudian sponge Amphimedon viridis. J Nat Prod 60:727-8
Ni, J; Mathews, M A; McCloskey, J A (1997) Collision-induced dissociation of polyprotonated oligonucleotides produced by electrospray ionization. Rapid Commun Mass Spectrom 11:535-40
Lowe, G; McCloskey, J A; Ni, J et al. (1996) A mass spectrometric investigation of the reaction between 4,4'-vinylenedipyridine bis[2,2':6',2""-terpyridine platinum(II)] and the self-complementary oligonucleotide d(CpGpTpApCpG). Bioorg Med Chem 4:1007-13
Bartlett, M G; McCloskey, J A; Manalili, S et al. (1996) The effect of backbone charge on the collision-induced dissociation of oligonucleotides. J Mass Spectrom 31:1277-83
Ni, J; Pomerantz, C; Rozenski, J et al. (1996) Interpretation of oligonucleotide mass spectra for determination of sequence using electrospray ionization and tandem mass spectrometry. Anal Chem 68:1989-99
Limbach, P A; Crain, P F; McCloskey, J A (1995) Characterization of oligonucleotides and nucleic acids by mass spectrometry. Curr Opin Biotechnol 6:96-102
Limbach, P A; Crain, P F; McCloskey, J A (1994) Summary: the modified nucleosides of RNA. Nucleic Acids Res 22:2183-96
Kowalak, J A; Pomerantz, S C; Crain, P F et al. (1993) A novel method for the determination of post-transcriptional modification in RNA by mass spectrometry. Nucleic Acids Res 21:4577-85

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