7-Hydroxycoumarins Are Affinity-Based Fluorescent Probes for Competitive Binding Studies of Macrophage Migration Inhibitory Factor
| العنوان: | 7-Hydroxycoumarins Are Affinity-Based Fluorescent Probes for Competitive Binding Studies of Macrophage Migration Inhibitory Factor |
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| المؤلفون: | Frank J. Dekker, Gerrit J. Poelarends, Zhangping Xiao, Shanshan Song, Barbro N. Melgert, Robbert H. Cool, Wim J. Quax, Ronald van Merkerk, Petra E van der Wouden, Deng Chen, Anna K. H. Hirsch, Ramon van der Vlag |
| المساهمون: | Chemical and Pharmaceutical Biology, Molecular Pharmacology, Chemical Biology 2, Biopharmaceuticals, Discovery, Design and Delivery (BDDD), Nanotechnology and Biophysics in Medicine (NANOBIOMED), Medicinal Chemistry and Bioanalysis (MCB) |
| المصدر: | Journal of medicinal chemistry United States Journal of Medicinal Chemistry, 63(20), 11920-11933. AMER CHEMICAL SOC Journal of Medicinal Chemistry |
| بيانات النشر: | American Chemical Society, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Models, Molecular, medicine.medical_treatment, animal diseases, INVASION, 01 natural sciences, Assays, Drug Discovery, Imaging probes, Enzyme Inhibitors, chemistry.chemical_classification, 0303 health sciences, Molecular Structure, biology, DERIVATIVES, Chemistry, Biological activity, respiratory system, CANCER, Intramolecular Oxidoreductases, COUMARIN, TARGET, Cytokine, Biochemistry, Molecular Medicine, MIF ENZYMATIC-ACTIVITY, chemical and pharmacologic phenomena, TAUTOMERASE INHIBITORS, Peptides and proteins, Binding, Competitive, Article, Fluorescence, Structure-Activity Relationship, 03 medical and health sciences, medicine, otorhinolaryngologic diseases, Humans, Structure–activity relationship, STRUCTURAL FEATURES, Umbelliferones, Macrophage Migration-Inhibitory Factors, Fluorescent Dyes, 030304 developmental biology, A549 cell, Dose-Response Relationship, Drug, Inhibitors, Active site, Enzyme assay, biological factors, 0104 chemical sciences, CYTOKINE, 010404 medicinal & biomolecular chemistry, Enzyme, DISCOVERY, biology.protein, Macrophage migration inhibitory factor |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0022-2623 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7d1eb77fe69b2442150e2afb9f15b7fd https://hdl.handle.net/10033/623224 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7d1eb77fe69b2442150e2afb9f15b7fd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00222623 |
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