31338-28-0Relevant academic research and scientific papers
In Situ Assembly of Choline Acetyltransferase Ligands by a Hydrothiolation Reaction Reveals Key Determinants for Inhibitor Design
Wiktelius, Daniel,Allgardsson, Anders,Bergstr?m, Tomas,Hoster, Norman,Akfur, Christine,Forsgren, Nina,Lejon, Christian,Hedenstr?m, Mattias,Linusson, Anna,Ekstr?m, Fredrik
, p. 813 - 819 (2021)
The potential drug target choline acetyltransferase (ChAT) catalyses the production of the neurotransmitter acetylcholine in cholinergic neurons, T-cells, and B-cells. Herein, we show that arylvinylpyridiniums (AVPs), the most widely studied class of ChAT inhibitors, act as substrate in an unusual coenzyme A-dependent hydrothiolation reaction. This in situ synthesis yields an adduct that is the actual enzyme inhibitor. The adduct is deeply buried in the active site tunnel of ChAT and interactions with a hydrophobic pocket near the choline binding site have major implications for the molecular recognition of inhibitors. Our findings clarify the inhibition mechanism of AVPs, establish a drug modality that exploits a target-catalysed reaction between exogenous and endogenous precursors, and provide new directions for the development of ChAT inhibitors with improved potency and bioactivity.
Styryl dyes. Synthesis and study of the solid-state [2+2] autophotocycloaddition by NMR spectroscopy and X-ray diffraction
Vedernikov,Kuz'mina,Sazonov,Lobova,Loginov,Churakov,Strelenko,Howard,Alfimov,Gromov
, p. 1860 - 1883 (2008/09/20)
New styryl dyes of the pyridine and benzothiazole series were synthesized with the aim of investigating the solid-state [2+2] autophotocycloaddition (PCA) reaction. The 1H NMR spectroscopy showed that for most of the compounds under study, the
Flexible N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogues: Synthesis and monoamine oxidase catalyzed bioactivation
Efange,Michelson,Remmel,Boudreau,Dutta,Freshler
, p. 3133 - 3138 (2007/10/02)
Eighteen analogues of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were synthesized and evaluated as substrates of monoamine oxidase. In general, the flexible analogues, characterized by the presence of a methylene (or ethylene) bridge between the aryl/heteroaryl and tetrahydropyridyl moieties, were better substrates of the enzyme than the conformationally restricted MPTP. It is suggested that the increased oxidative activity of these flexible analogues reflects enhanced binding due to the ability of the C-4-aryl/heteroaryl substituent to gain access to a hydrophobic pocket within the substrate binding site.
