20.500.12556/RUL-125368 Development of potent reversible selective inhibitors of butyrylcholinesterase as fluorescent probes 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. butyrylcholinesterase inhibitor probe fluorescence patogeneza Alzheimerjeve bolezni butiriliholinesteraza zaviralci true false true Angleški jezik Slovenski jezik Članek v reviji 2021-03-12 12:03:59 2021-03-12 12:04:00 2022-09-05 03:50:25 0000-00-00 00:00:00 2020 0 0 Str. 498-505 iss. 1 Vol. 35 2020 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.894+616.892.3:615.2 1475-6366 10.1080/14756366.2019.1710502 4869233 512255001 RAZ_Pajk_Stane_2020.pdf RAZ_Pajk_Stane_2020.pdf 1 409B34DEEF5881A8DE2B34B90529B0E9 83751c723348c7acd55e495ad57411cd18a879aba3c20a2835bbf400e4f49de5 e4e7b405-a1bb-11eb-a523-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=142284 https://www.tandfonline.com/doi/full/10.1080/14756366.2019.1710502 1 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=141063 Fakulteta za farmacijo Medicinska fakulteta 0 0 0