Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/119855
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dc.contributor.authorNguyen, G.en
dc.contributor.authorTran, T.en
dc.contributor.authorPodgorski, M.en
dc.contributor.authorBell, S.en
dc.contributor.authorSupuran, C.en
dc.contributor.authorDonald, W.en
dc.date.issued2019en
dc.identifier.citationACS Central Science, 2019; 5(2):308-318en
dc.identifier.issn2374-7943en
dc.identifier.issn2374-7951en
dc.identifier.urihttp://hdl.handle.net/2440/119855-
dc.description.abstractElectrospray ionization (ESI) mass spectrometry (MS) is a crucial method for rapidly determining the interactions between small molecules and proteins with ultrahigh sensitivity. However, nonvolatile molecules and salts that are often necessary to stabilize the native structures of protein-ligand complexes can readily adduct to protein ions, broaden spectral peaks, and lower signal-to-noise ratios in native MS. ESI emitters with narrow tip diameters (∼250 nm) were used to significantly reduce the extent of adduction of salt and nonvolatile molecules to protein complexes to more accurately measure ligand-protein binding constants than by use of conventional larger-bore emitters under these conditions. As a result of decreased salt adduction, peaks corresponding to protein-ligand complexes that differ in relative molecular weight by as low as 0.06% can be readily resolved. For low-molecular-weight anion ligands formed from sodium salts, anion-bound and unbound protein ions that differ in relative mass by 0.2% were completely baseline resolved using nanoscale emitters, which was not possible under these conditions using conventional emitters. Owing to the improved spectral resolution obtained using narrow-bore emitters and an analytically derived equation, K d values were simultaneously obtained for at least six ligands to a single druggable protein target from one spectrum for the first time. This research suggests that ligand-protein binding constants can be directly and accurately measured from solutions with high concentrations of nonvolatile buffers and salts by native MS.en
dc.description.statementofresponsibilityGiang T.H. Nguyen, Thinh N. Tran, Matthew N. Podgorski, Stephen G. Bell, Claudiu T. Supuran, and William A. Donalden
dc.language.isoenen
dc.publisherAmerican Chemical Societyen
dc.rights© 2019 American Chemical Society This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.en
dc.titleNanoscale ion emitters in native mass spectrometry for measuring ligand–protein binding affinitiesen
dc.typeJournal articleen
dc.identifier.rmid0030107679en
dc.identifier.doi10.1021/acscentsci.8b00787en
dc.relation.granthttp://purl.org/au-research/grants/arc/DP160102681en
dc.identifier.pubid457958-
pubs.library.collectionChemistry publicationsen
pubs.library.teamDS14en
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
dc.identifier.orcidPodgorski, M. [0000-0003-3238-8735]en
dc.identifier.orcidBell, S. [0000-0002-7457-9727]en
Appears in Collections:Chemistry publications

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