NDLI: Understanding Gas Phase Modifier Interactions in Rapid Analysis by Differential Mobility-Tandem Mass Spectrometry

Content Provider	Springer Nature Link
Author	Kafle, Amol Coy, Stephen L. Wong, Bryan M. Fornace, Albert J. Glick, James J. Vouros, Paul
Copyright Year	2014
Abstract	A systematic study involving the use and optimization of gas-phase modifiers in quantitative differential mobility-mass spectrometry (DMS-MS) analysis is presented using nucleoside-adduct biomarkers of DNA damage as an important reference point for analysis in complex matrices. Commonly used polar protic and polar aprotic modifiers have been screened for use against two deoxyguanosine adducts of DNA: N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-4-ABP) and N-(deoxyguanosin-8-y1)-2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (dG-C8-PhIP). Particular attention was paid to compensation voltage (CoV) shifts, peak shapes, and product ion signal intensities while optimizing the DMS-MS conditions. The optimized parameters were then applied to rapid quantitation of the DNA adducts in calf thymus DNA. After a protein precipitation step, adduct levels corresponding to less than one modification in 10$^{6}$ normal DNA bases were detected using the DMS-MS platform. Based on DMS fundamentals and ab initio thermochemical results, we interpret the complexity of DMS modifier responses in terms of thermal activation and the development of solvent shells. At very high bulk gas temperature, modifier dipole moment may be the most important factor in cluster formation and cluster geometry, but at lower temperatures, multi-neutral clusters are important and less predictable. This work provides a useful protocol for targeted DNA adduct quantitation and a basis for future work on DMS modifier effects.
Starting Page	1098
Ending Page	1113
Page Count	16
File Format	PDF
ISSN	10440305
Journal	Journal of The American Society for Mass Spectrometry
Volume Number	25
Issue Number	7
e-ISSN	18791123
Language	English
Publisher	Springer US
Publisher Date	2014-01-23
Publisher Institution	The American Society for Mass Spectrometry
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Differential ion mobility DMS FAIMS DNA adducts Gas phase interactions Modifiers Quantitation Kinetics Ion-polar molecule clustering Analytical Chemistry Biotechnology Organic Chemistry Proteomics Bioinformatics
Content Type	Text
Resource Type	Article
Subject	Spectroscopy Structural Biology

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