Abstract

The analytical potential of mass spectrometry will be developed for applications involving analytical and structural studies of nucleic acid-derived materials. Thermospray LC/MS studies will be extended to include microcolumn LC techniques which will permit post-column reactions and solvent manipulations prior to vaporization. Tandem mass spectrometry, employing low-energy collision-induced dissociation of model nucleosides and nucleotides will be studied with regard to mode of primary ionization, optimization of sensitivity, and efficient utilization of tandem scan functions for sample-limited measurements. Emphasis will be placed on methods for microscale characterization of constituents of unknown structure directly in mixtures. Applications of the methods developed will be made to model mixture systems, including detection of modified nucleosides in enzymatic hydrolysates of nucleic acids.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM021584-15
Application #
3270577
Study Section
(SSS)
Project Start
1978-01-01
Project End
1992-12-31
Budget Start
1989-01-01
Budget End
1989-12-31
Support Year
15
Fiscal Year
1989
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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