2,2,2-Trifluoroethyl 6-thio-β-d-glucopyranoside as a selective tag for cysteines in proteins

A synthetic route to a trifluoromethyl and thiol containing glucose derivative (2,2,2-trifluoroethyl 6-thio-β-d-glucopyranoside) is presented, which is based on microwave-assisted Fischer glycosylation under increased pressure. This water-soluble, neutral thiol-compound can be used to selectively introduce a fluorine probe for 19F NMR spectroscopy on cysteines in proteins. It can be attached under mild conditions in an aqueous environment without the risk of denaturing the protein. This tag has been applied to determine the redox-state of two cysteine residues in a bacterial transcription activator. Qualitative information about the solvent accessibility can be obtained from F-19 solvent PREs.