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Liquid chromatography - tandem mass ...
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Sharma, Vaneet Kumar.
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Liquid chromatography - tandem mass spectrometry methods for the analysis of isomeric oligonucleotide adducts.
Record Type:
Language materials, printed : Monograph/item
Title/Author:
Liquid chromatography - tandem mass spectrometry methods for the analysis of isomeric oligonucleotide adducts./
Author:
Sharma, Vaneet Kumar.
Description:
253 p.
Notes:
Source: Dissertation Abstracts International, Volume: 74-05(E), Section: B.
Contained By:
Dissertation Abstracts International74-05B(E).
Subject:
Chemistry, Analytical. -
Online resource:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3547560
ISBN:
9781267823205
Liquid chromatography - tandem mass spectrometry methods for the analysis of isomeric oligonucleotide adducts.
Sharma, Vaneet Kumar.
Liquid chromatography - tandem mass spectrometry methods for the analysis of isomeric oligonucleotide adducts.
- 253 p.
Source: Dissertation Abstracts International, Volume: 74-05(E), Section: B.
Thesis (Ph.D.)--Northeastern University, 2013.
The main theme of this dissertation is to develop liquid chromatography electrospray ionization tandem mass spectrometry-based methodologies to investigate isomeric oligonucleotide adducts. One of the important aspects of the work presented is the use of in-house fabricated polymeric monolithic capillary columns, poly(styrene-divinyl benzene). Another important aspect lies in the development and incorporation of additional capabilities into the in-house designed peak assignment software, GenoMass.
ISBN: 9781267823205Subjects--Topical Terms:
586156
Chemistry, Analytical.
Liquid chromatography - tandem mass spectrometry methods for the analysis of isomeric oligonucleotide adducts.
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Liquid chromatography - tandem mass spectrometry methods for the analysis of isomeric oligonucleotide adducts.
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253 p.
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Source: Dissertation Abstracts International, Volume: 74-05(E), Section: B.
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Adviser: Paul Vouros.
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Thesis (Ph.D.)--Northeastern University, 2013.
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The main theme of this dissertation is to develop liquid chromatography electrospray ionization tandem mass spectrometry-based methodologies to investigate isomeric oligonucleotide adducts. One of the important aspects of the work presented is the use of in-house fabricated polymeric monolithic capillary columns, poly(styrene-divinyl benzene). Another important aspect lies in the development and incorporation of additional capabilities into the in-house designed peak assignment software, GenoMass.
520
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In Chapter 1, an introduction to carcinogenic adducts and their potential role in carcinogenesis is presented. Also presented is the background on various techniques used for the identification & characterization of DNA adducts. In addition analytical challenges and limitations to the analysis of the oligonucleotide adducts sequence is presented. Briefly, a number of analytical techniques, i.e. 32P-postlabeling, immunoassay, fluorescence, etc have been introduced but emphasis has been on the emergence of mass spectrometry based techniques via the hyphenation of liquid chromatography for the analysis of DNA adducts. The need to develop mass spectrometry based software to sequence nucleic acids is also presented.
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In Chapter 2, the development of an ion-pair reversed-phase liquid chromatography electrospray ionization tandem mass spectrometry (IP-RPLC-ESI-MS/MS) method for separation of isomeric modified oligonucleotide using a monolithic poly(styrene-divinylbenzene) capillary column is presented. The effects of different ion pairing reagents (IPR), their concentration, mobile phase additives and conditions were evaluated towards achieving the highest possible resolution and chromatographic separation of isomeric oligonucleotide. Ion pairing reagents and mobile phase conditions were evaluated using as model N-acetylaminofluorene [AAF] adducted ss-oligonucleotide (CCC CGA GCA ATC TCA AT).
520
$a
In Chapter 3, the developed IP-RPLC-ESI-MS/MS method was applied for the mapping of sites of base modification of various carcinogenic adducted oligonucleotide fragments individually or in a mixture. The optimized mobile phase conditions were further evaluated under nanoLC-nanoESI conditions to investigate the sequence selectivity of different carcinogens for a region of exon 5 of p53 gene, which contains the mutational hot-spot codons (5'P- ACC155 CGC156 GTC 157 CGC158 GC/ 5&feet;- GCG CGG ACG CGG GT ). The carcinogens selected for the study were N-acetoxy-2-acetylaminofluorene (AAAF), N-Hydroxy-4-aminobiphenyl (N-OH-4-ABP) and (+)-anti-7r,8t-dihydroxy-9t,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene ((+)-anti-BPDE).
520
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In Chapter 4, The in-house developed GenoMass software was used for the computational data interpretation of the MS/MS spectra of oligonucleotide adducts. GenoMass is a peak assignment algorithm that performs computational analysis of collision-induced dissociation (CID) fragments. The performance of this tandem mass spectrometry based GenoMass software was evaluated for various oligonucleotide adducts, cytosine methyl modified (-CpGs) oligonucleotide and Phosphorothioates (S-oligo) individually or in a mixture.
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In Chapter 5, Future research perspectives of utilizing cell free circulating DNA for mass spectrometry based analysis are presented. Further recommendations regarding improvements in GenoMass software are listed. (Abstract shortened by UMI.).
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School code: 0160.
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http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3547560
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