Analysis of mononucleotides by tandem mass spectrometry: investigation of fragmentation pathways for phosphate- and ribose-modified nucleotide analogues

Abstract Synthetic nucleotide and nucleic acid analogues are useful research tools and modern therapeutics. Hence, methods for the rapid and unambiguous identification of mononucleotides derived from organic syntheses or biological materials are of broad interest. Here, we analysed over 150 mononucl...

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Autores principales:	Dominika Strzelecka, Sebastian Chmielinski, Sylwia Bednarek, Jacek Jemielity, Joanna Kowalska
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0b5a57dcedb74c0bbaf4eba0ca5baf1e
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spelling	oai:doaj.org-article:0b5a57dcedb74c0bbaf4eba0ca5baf1e2021-12-02T15:05:47ZAnalysis of mononucleotides by tandem mass spectrometry: investigation of fragmentation pathways for phosphate- and ribose-modified nucleotide analogues10.1038/s41598-017-09416-62045-2322https://doaj.org/article/0b5a57dcedb74c0bbaf4eba0ca5baf1e2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09416-6https://doaj.org/toc/2045-2322Abstract Synthetic nucleotide and nucleic acid analogues are useful research tools and modern therapeutics. Hence, methods for the rapid and unambiguous identification of mononucleotides derived from organic syntheses or biological materials are of broad interest. Here, we analysed over 150 mononucleotides (mostly nucleoside 5′-mono-, 5′-di-, and 5′-triphosphates) and their structurally related nucleobase-, phosphate-, and ribose-modified analogues by electrospray tandem mass spectrometry (ESI/MS/MS), identifying characteristic fragmentation ions that may be helpful in structure determination. While positive-ion mode yielded fragments derived mainly from nucleobases, negative-ion mode provided insight into the structures of phosphoryl and phosphoribosyl moieties, enabling the determination of structural features such as the number of phosphate groups and the presence of ribose or phosphate substitutions. Based on these data, we proposed fragmentation pathways that were confirmed by experiments with [18O]-isotopologues. We demonstrated the utility of ESI(−)/MS/MS in the analysis of structurally related compounds by analysing isomeric and isobaric nucleotides and applying ESI(−)/MS/MS to rapid identification of nucleotide synthesis products. We formulated general rules regarding nucleotide structure–fragmentation pattern relationships and indicating characteristic fragmentation ions for the interpretation of ESI(−)/MS/MS spectra of nucleotides and their analogues. The ESI(−)/MS/MS spectra of all nucleotides are available in an on-line database, msTide, at www.msTide-db.com.Dominika StrzeleckaSebastian ChmielinskiSylwia BednarekJacek JemielityJoanna KowalskaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Dominika Strzelecka Sebastian Chmielinski Sylwia Bednarek Jacek Jemielity Joanna Kowalska Analysis of mononucleotides by tandem mass spectrometry: investigation of fragmentation pathways for phosphate- and ribose-modified nucleotide analogues
description	Abstract Synthetic nucleotide and nucleic acid analogues are useful research tools and modern therapeutics. Hence, methods for the rapid and unambiguous identification of mononucleotides derived from organic syntheses or biological materials are of broad interest. Here, we analysed over 150 mononucleotides (mostly nucleoside 5′-mono-, 5′-di-, and 5′-triphosphates) and their structurally related nucleobase-, phosphate-, and ribose-modified analogues by electrospray tandem mass spectrometry (ESI/MS/MS), identifying characteristic fragmentation ions that may be helpful in structure determination. While positive-ion mode yielded fragments derived mainly from nucleobases, negative-ion mode provided insight into the structures of phosphoryl and phosphoribosyl moieties, enabling the determination of structural features such as the number of phosphate groups and the presence of ribose or phosphate substitutions. Based on these data, we proposed fragmentation pathways that were confirmed by experiments with [18O]-isotopologues. We demonstrated the utility of ESI(−)/MS/MS in the analysis of structurally related compounds by analysing isomeric and isobaric nucleotides and applying ESI(−)/MS/MS to rapid identification of nucleotide synthesis products. We formulated general rules regarding nucleotide structure–fragmentation pattern relationships and indicating characteristic fragmentation ions for the interpretation of ESI(−)/MS/MS spectra of nucleotides and their analogues. The ESI(−)/MS/MS spectra of all nucleotides are available in an on-line database, msTide, at www.msTide-db.com.
format	article
author	Dominika Strzelecka Sebastian Chmielinski Sylwia Bednarek Jacek Jemielity Joanna Kowalska
author_facet	Dominika Strzelecka Sebastian Chmielinski Sylwia Bednarek Jacek Jemielity Joanna Kowalska
author_sort	Dominika Strzelecka
title	Analysis of mononucleotides by tandem mass spectrometry: investigation of fragmentation pathways for phosphate- and ribose-modified nucleotide analogues
title_short	Analysis of mononucleotides by tandem mass spectrometry: investigation of fragmentation pathways for phosphate- and ribose-modified nucleotide analogues
title_full	Analysis of mononucleotides by tandem mass spectrometry: investigation of fragmentation pathways for phosphate- and ribose-modified nucleotide analogues
title_fullStr	Analysis of mononucleotides by tandem mass spectrometry: investigation of fragmentation pathways for phosphate- and ribose-modified nucleotide analogues
title_full_unstemmed	Analysis of mononucleotides by tandem mass spectrometry: investigation of fragmentation pathways for phosphate- and ribose-modified nucleotide analogues
title_sort	analysis of mononucleotides by tandem mass spectrometry: investigation of fragmentation pathways for phosphate- and ribose-modified nucleotide analogues
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0b5a57dcedb74c0bbaf4eba0ca5baf1e
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Analysis of mononucleotides by tandem mass spectrometry: investigation of fragmentation pathways for phosphate- and ribose-modified nucleotide analogues

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