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dc.contributor.authorXiao, Zhangping
dc.contributor.authorChen, Deng
dc.contributor.authorSong, Shanshan
dc.contributor.authorvan der Vlag, Ramon
dc.contributor.authorvan der Wouden, Petra E
dc.contributor.authorvan Merkerk, Ronald
dc.contributor.authorCool, Robbert H
dc.contributor.authorHirsch, Anna K H
dc.contributor.authorMelgert, Barbro N
dc.contributor.authorQuax, Wim J
dc.contributor.authorPoelarends, Gerrit J
dc.contributor.authorDekker, Frank J
dc.date.accessioned2022-06-14T09:21:56Z
dc.date.available2022-06-14T09:21:56Z
dc.date.issued2020-10-13
dc.date.submitted2020-07-06
dc.identifier.pmid32940040
dc.identifier.doi10.1021/acs.jmedchem.0c01160
dc.identifier.urihttp://hdl.handle.net/10033/623224
dc.description.abstractMacrophage migration inhibitory factor (MIF) is a cytokine with key roles in inflammation and cancer, which qualifies it as a potential drug target. Apart from its cytokine activity, MIF also harbors enzyme activity for keto-enol tautomerization. MIF enzymatic activity has been used for identification of MIF binding molecules that also interfere with its biological activity. However, MIF tautomerase activity assays are troubled by irregularities, thus creating a need for alternative methods. In this study, we identified a 7-hydroxycoumarin fluorophore with high affinity for the MIF tautomerase active site (Ki = 18 ± 1 nM) that binds with concomitant quenching of its fluorescence. This property enabled development of a novel competition-based assay format to quantify MIF binding. We also demonstrated that the 7-hydroxycoumarin fluorophore interfered with the MIF-CD74 interaction and inhibited proliferation of A549 cells. Thus, we provide a high-affinity MIF binder as a novel tool to advance MIF-oriented research.en_US
dc.language.isoenen_US
dc.publisherAmerican Chemical Societyen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.title7-Hydroxycoumarins Are Affinity-Based Fluorescent Probes for Competitive Binding Studies of Macrophage Migration Inhibitory Factor.en_US
dc.typeArticleen_US
dc.identifier.eissn1520-4804
dc.identifier.journalJournal of medicinal chemistryen_US
dc.source.volume63
dc.source.issue20
dc.source.beginpage11920
dc.source.endpage11933
refterms.dateFOA2022-06-14T09:21:56Z
dc.source.journaltitleJournal of medicinal chemistry
dc.source.countryUnited States


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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International