Pajk_2020_J.Enzyme.Inhib.Med.Chem_35_498

Reference

Title : Development of potent reversible selective inhibitors of butyrylcholinesterase as fluorescent probes - Pajk_2020_J.Enzyme.Inhib.Med.Chem_35_498
Author(s) : Pajk S , Knez D , Kosak U , Zorovic M , Brazzolotto X , Coquelle N , Nachon F , Colletier JP , Zivin M , Stojan J , Gobec S
Ref : J Enzyme Inhib Med Chem , 35 :498 , 2020
Abstract :

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.

PubMedSearch : Pajk_2020_J.Enzyme.Inhib.Med.Chem_35_498
PubMedID: 31914836
Gene_locus related to this paper: human-BCHE

Related information

Inhibitor 6RUA-3a    JU5    JUB
Gene_locus 6RUA-3a    JU5    JUB    human-BCHE
Structure 6RUA-3a    JU5    JUB    human-BCHE    6RUA    6R6W    6R6V

Citations formats

Pajk S, Knez D, Kosak U, Zorovic M, Brazzolotto X, Coquelle N, Nachon F, Colletier JP, Zivin M, Stojan J, Gobec S (2020)
Development of potent reversible selective inhibitors of butyrylcholinesterase as fluorescent probes
J Enzyme Inhib Med Chem 35 :498

Pajk S, Knez D, Kosak U, Zorovic M, Brazzolotto X, Coquelle N, Nachon F, Colletier JP, Zivin M, Stojan J, Gobec S (2020)
J Enzyme Inhib Med Chem 35 :498