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Retro Diels-Alder fragmentation of fulvene-maleimide bioconjugates for mass spectrometric detection of biomolecules

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dc.contributor.authorStevens, K.G.
dc.contributor.authorMcFarlane, L.O.
dc.contributor.authorPlatts, K.
dc.contributor.authorO'Brien-Simpson, N.
dc.contributor.authorLi, W.
dc.contributor.authorBlencowe, A.
dc.contributor.authorTrim, P.J.
dc.contributor.authorPukala, T.L.
dc.date.issued2021
dc.description.abstractDiels-Alder chemistry is a well-explored avenue for the synthesis of bioactive materials; however, its potential applications have recently expanded following the development of reactions that can be performed in buffered aqueous environments at low temperatures, including fulvene-maleimide [4 + 2] cycloadditions. In this study, we synthesized two novel amine-reactive fulvene linkers to demonstrate the application of this chemistry for generating mass spectrometry-cleavable labels ("mass tags"), which can be used for the labeling and detection of proteins. Successful conjugation of these linkers to maleimide-labeled peptides was observed at low temperatures in phosphate-buffered saline, allowing the non-destructive modification of proteins with such mass tags. The labile nature of fulvene-maleimide adducts in the gas phase also makes them suitable for both matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI) mass spectrometric analysis. Unlike previous examples of MALDI mass tags, we show that fulvene-maleimide cycloaddition adducts fragment predictably upon gas-phase activation without the need for bulky photocleavable groups. Further exploration of this chemistry could therefore lead to new approaches for mass spectrometry-based bioassays.
dc.description.statementofresponsibilityKatherine G. Stevens, Lewis O. McFarlane, Kirsten Platts, Neil O’Brien-Simpson, Wenyi Li, Anton Blencowe, Paul J. Trim, and Tara L. Pukala
dc.identifier.citationAnalytical Chemistry, 2021; 93(36):12204-12212
dc.identifier.doi10.1021/acs.analchem.1c00193
dc.identifier.issn0003-2700
dc.identifier.issn1520-6882
dc.identifier.orcidStevens, K.G. [0000-0001-9552-7670]
dc.identifier.orcidMcFarlane, L.O. [0000-0002-9741-9769]
dc.identifier.orcidBlencowe, A. [0000-0002-7630-4874]
dc.identifier.orcidTrim, P.J. [0000-0001-8734-3433]
dc.identifier.orcidPukala, T.L. [0000-0001-7391-1436]
dc.identifier.urihttps://hdl.handle.net/2440/133040
dc.language.isoen
dc.publisherAmerican Chemical Society
dc.relation.granthttp://purl.org/au-research/grants/arc/DP170102033
dc.rights© 2021 American Chemical Society
dc.source.urihttps://doi.org/10.1021/acs.analchem.1c00193
dc.subjectMaleimides
dc.subject.meshMaleimides
dc.subject.meshCyclopentanes
dc.subject.meshPeptides
dc.subject.meshSpectrometry, Mass, Electrospray Ionization
dc.subject.meshSpectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
dc.titleRetro Diels-Alder fragmentation of fulvene-maleimide bioconjugates for mass spectrometric detection of biomolecules
dc.typeJournal article
pubs.publication-statusPublished

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