Development of potent reversible selective inhibitors of butyrylcholinesterase as fluorescent probes
| العنوان: | Development of potent reversible selective inhibitors of butyrylcholinesterase as fluorescent probes |
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| المؤلفون: | Xavier Brazzolotto, Florian Nachon, Marko Živin, Jure Stojan, Maja Zorović, Damijan Knez, Jacques-Philippe Colletier, Urban Košak, Stanislav Gobec, Stane Pajk, Nicolas Coquelle |
| المساهمون: | Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut Laue-Langevin (ILL), Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Institut de Recherche Biomédicale des Armées (IRBA), ILL, University of Ljubljana, Faculty of Pharmacy, Askerceva 7, 1000 Ljubljana, Slovenia, Faculty of Pharmacy, University of Ljubljana, Département de Toxicologie et Risques Chimiques, Institute of Biochemistry, Faculty of Medicine |
| المصدر: | Journal of Enzyme Inhibition and Medicinal Chemistry Journal of Enzyme Inhibition and Medicinal Chemistry, 2020, 35 (1), pp.498-505. ⟨10.1080/14756366.2019.1710502⟩ Journal of Enzyme Inhibition and Medicinal Chemistry, Informa Healthcare, 2020, 35 (1), pp.498-505. ⟨10.1080/14756366.2019.1710502⟩ Journal of enzyme inhibition and medicinal chemistry, vol. 35, no. 1, pp. 498-505, 2020. Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 35, Iss 1, Pp 498-505 (2020) |
| بيانات النشر: | HAL CCSD, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Models, Molecular, [SDV]Life Sciences [q-bio], Crystallography, X-Ray, 01 natural sciences, Mice, chemistry.chemical_compound, Drug Discovery, MESH: Animals, Butyrylcholinesterase, chemistry.chemical_classification, zaviralci, Molecular Structure, biology, MESH: Butyrylcholinesterase, General Medicine, MESH: Fluorescent Dyes, Fluorescence, Acetylcholinesterase, MESH: Amides, 3. Good health, inhibitor, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Fluorescence intensity, Biochemistry, butyrylcholinesterase, fluorescence, patogeneza Alzheimerjeve bolezni, MESH: Cholinesterase Inhibitors, MESH: Models, Molecular, Research Paper, MESH: Molecular Structure, Mixed inhibition, RM1-950, probe, butiriliholinesteraza, Hydrolase, Animals, Humans, [CHIM]Chemical Sciences, udc:616.894+616.892.3:615.2, MESH: Mice, Fluorescent Dyes, Pharmacology, MESH: Humans, 010405 organic chemistry, Active site, MESH: Crystallography, X-Ray, Amides, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, Enzyme, chemistry, biology.protein, Therapeutics. Pharmacology, Cholinesterase Inhibitors |
| الوصف: | International audience; Brain butyrylcholinesterase (BChE) is an attractive target for drugs designed for the treatment of Alzheimer’s disease (AD) in its advanced stages. It also potentially represents a biomarker for progression of this disease. Based on the crystal structure of previously described highly potent, reversible, and selective BChE inhibitors, we have developed the fluorescent probes that are selective towards human BChE. The most promising probes also maintain their inhibition of BChE in the low nanomolar range with high selectivity over acetylcholinesterase. Kinetic studies of probes reveal a reversible mixed inhibition mechanism, with binding of these fluorescent probes to both the free and acylated enzyme. Probes show environment-sensitive emission, and additionally, one of them also shows significant enhancement of fluorescence intensity upon binding to the active site of BChE. Finally, the crystal structures of probes in complex with human BChE are reported, which offer an excellent base for further development of this library of compounds. |
| وصف الملف: | application/pdf; text/url |
| اللغة: | English |
| تدمد: | 1475-6366 1475-6374 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::346bbfead7d353e2e74735bc335c4593 https://hal.science/hal-03014299/file/Pajk2020.pdf |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....346bbfead7d353e2e74735bc335c4593 |
| قاعدة البيانات: | OpenAIRE |
PDF full text from Publisher | تدمد: | 14756366 14756374 |
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