title: Synthesis, inhibition properties, and theoretical study of the new nanomolar trehalase inhibitor 1-thiatrehazolin: towards a structural understanding of trehazolin inhibition.
abstract: A new trehazolin analogue, 1-thiatrehazolin, has been synthesized from carbohydrate precursors by a highly efficient route based on our previously developed ketone/oxime ether reductive carbocyclization reaction for the construction of the cyclitol ring and an intramolecular nucleophilic displacement reaction for the construction of the thiazoline ring. 1-Thiatrehazolin is a very potent, slow, tight-binding trehalase inhibitor. A structural model for trehalase inhibition by trehazolin and its analogues, based on the experimental results and supported by theoretical calculations, is proposed.
authors.affiliation: Instituto de Química Orgánica General, CSIC, Juan de la Cierva 3, 28006 Madrid, Spain. jl.chiara@iqog.csic.es
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Chiara
authors.forename: Isabel
authors.initials: I
authors.lastname: Storch de Gracia
authors.forename: Angela
authors.initials: A
authors.lastname: García
authors.forename: Agatha
authors.initials: A
authors.lastname: Bastida
authors.forename: Sofía
authors.initials: S
authors.lastname: Bobo
authors.forename: María D
authors.initials: MD
authors.lastname: Martín-Ortega
mesh_terms: D000818:Animals; D004187:Disaccharides / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology; D008962:Models, Theoretical; D009005:Monosaccharides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013552:Swine; D014198:Trehalase / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: C502223:1-thiatrehazolin; D004187:Disaccharides; D004791:Enzyme Inhibitors; D009005:Monosaccharides; C071816:trehazolin; D014198:Trehalase