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Author Daems, E.; Dewaele, D.; Barylyuk, K.; De Wael, K.; Sobott, F.
Title Aptamer-ligand recognition studied by native ion mobility-mass spectrometry Type A1 Journal article
Year 2021 Publication Talanta Abbreviated Journal Talanta
Volume 224 Issue Pages 121917
Keywords A1 Journal article; AXES (Antwerp X-ray Analysis, Electrochemistry and Speciation)
Abstract The range of applications for aptamers, small oligonucleotide-based receptors binding to their targets with high specificity and affinity, has been steadily expanding. Our understanding of the mechanisms governing aptamer-ligand recognition and binding is however lagging, stymieing the progress in the rational design of new aptamers and optimization of the known ones. Here we demonstrate the capabilities and limitations of native ion mobility-mass spectrometry for the analysis of their higher-order structure and non-covalent interactions. A set of related cocaine-binding aptamers, displaying a range of folding properties and ligand binding affinities, was used as a case study in both positive and negative electrospray ionization modes. Using carefully controlled experimental conditions, we probed their conformational behavior and interactions with the high-affinity ligand quinine as a surrogate for cocaine. The ratios of bound and unbound aptamers in the mass spectra were used to rank them according to their apparent quinine-binding affinity, qualitatively matching the published ranking order. The arrival time differences between the free aptamer and aptamer-quinine complexes were consistent with a small ligand-induced conformational change, and found to inversely correlate with the affinity of binding. This mass spectrometry-based approach provides a fast and convenient way to study the molecular basis of aptamer-ligand recognition.
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Corporate Author Thesis
Publisher Place of Publication Editor
Language (up) Wos 000600787800122 Publication Date 2020-12-02
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0039-9140; 1873-3573 ISBN Additional Links UA library record; WoS full record; WoS citing articles
Impact Factor 4.162 Times cited Open Access OpenAccess
Notes Approved Most recent IF: 4.162
Call Number UA @ admin @ c:irua:174086 Serial 7490
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