Lehn JM

References (2)

Title : Grid-type Quaternary Metallosupramolecular Compounds Inhibit Human Cholinesterases through Dynamic Multivalent Interactions - Nachon_2022_Chembiochem_23_e202200456
Author(s) : Nachon F , Brazzolotto X , Dias J , Courageux C , Drozdz W , Cao XY , Stefankiewicz AR , Lehn JM
Ref : Chembiochem , 23 :e202200456 , 2022
Abstract : We report herein the implementation of coordination complexes containing two types of cationic moieties, i.e. pyridinium and ammonium quaternary salt, as potential inhibitors of human cholinesterase enzymes. Utilization of ligands containing NNO-coordination site and binding zinc metal ion allowed obtaining mono- and tetra-nuclear complexes with corner and grid structural type respectively, thus affecting the overall charge of the compounds (from +1 to +8). It enabled for the first time to examine the multivalency effect of metallosupramolecular species on their inhibitory abilities towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Importantly, resolution of the crystal structures of the obtained enzyme-substrate complexes provided a better understanding of the inhibition process at the molecular level.
ESTHER : Nachon_2022_Chembiochem_23_e202200456
PubMedSearch : Nachon_2022_Chembiochem_23_e202200456
PubMedID: 36193860
Gene_locus related to this paper: human-BCHE

Title : Dynamic deconvolution of a pre-equilibrated dynamic combinatorial library of acetylcholinesterase inhibitors - Bunyapaiboonsri_2001_Chembiochem_2_438
Author(s) : Bunyapaiboonsri T , Ramstrom O , Lohmann S , Lehn JM , Peng L , Goeldner M
Ref : Chembiochem , 2 :438 , 2001
Abstract : A dynamic combinatorial library composed of interconverting acylhydrazones has been generated and screened towards inhibition of acetylcholinesterase from the electric ray Torpedo marmorata. Starting from a small set (13) of initial hydrazide and aldehyde building blocks, a library containing possibly 66 different species was obtained in a single operation. Of all possible acylhydrazones formed, active compounds containing two terminal cationic recognition groups separated by an appropriate distance, permitting two-site binding, could be rapidly identified by using a dynamic deconvolution--screening procedure, based on the sequential removal of starting building blocks. A very potent bis-pyridinium inhibitor (K(i)=1.09 nM, alphaK(i)=2.80 nM) was selected from the process and the contribution of various structural features to inhibitory potency was evaluated.
ESTHER : Bunyapaiboonsri_2001_Chembiochem_2_438
PubMedSearch : Bunyapaiboonsri_2001_Chembiochem_2_438
PubMedID: 11828475