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7-Hydroxycoumarins are Affinity-based Fluorescent Probes for Competitive Binding Studies of Macrophage Migration Inhibitory Factor

Xiao, Z., Chen, D., Song, S., van der Vlag, R., van der Wouden, P. E., van Merkerk, R., Cool, R., Hirsch, A. K. H., Melgert, B., Quax, W. J., Poelarends, G. J. & Dekker, F. J., 17-Sep-2020, In : Journal of Medicinal Chemistry. 20, p. 11920-11933

Research output: Contribution to journalArticleAcademicpeer-review

Macrophage 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.

Original languageEnglish
Pages (from-to)11920-11933
JournalJournal of Medicinal Chemistry
Issue number20
Publication statusE-pub ahead of print - 17-Sep-2020

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