Abstract

The analytical potential of mass spectrometry will be developed for applications to the constituents of nucleic acids. Directly combined high performance liquid chromatography-mass spectrometry, utilizing the thermospray ionization technique, will be evaluated with model nucleosides and in the analysis of enzymatic hydrolysates of transfer RNA. The utility of fast atom bombardment, a new method for vaporization and ionization of large and polar molecules, will be explored as a method of detection of complex nucleosides in hydrolysates of nucleic acids. Gas chromatography-mass spectrometry with stable isotope dilution will be further developed and applied to the low-level quantitative measurement of methylated bases in DNA. Computer programs will be written for the analysis of photographically recorded high resolution mass spectra, particularly for applications to complex mixtures.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM021584-12
Application #
3270575
Study Section
(SSS)
Project Start
1978-01-01
Project End
1987-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
12
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Utah
Department
Type
Schools of Pharmacy
DUNS #
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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