Synthesis, inhibition properties, and theoretical study of the new nanomolar trehalase inhibitor 1-thiatrehazolin: towards a structural understanding of trehazolin inhibition.
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.
Chiara
Jose Luis
JL
Instituto de Química Orgánica General, CSIC, Juan de la Cierva 3, 28006 Madrid, Spain. jl.chiara@iqog.csic.es
Storch de Gracia
Isabel
I
García
Angela
A
Bastida
Agatha
A
Bobo
Sofía
S
Martín-Ortega
María D
MD
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
C502223:1-thiatrehazolin; D004187:Disaccharides; D004791:Enzyme Inhibitors; D009005:Monosaccharides; C071816:trehazolin; D014198:Trehalase