title: A "Smart" ¹²⁸Xe NMR Biosensor for pH-Dependent Cell Labeling.
abstract: Here we present a "smart" xenon-129 NMR biosensor that undergoes a peptide conformational change and labels cells in acidic environments. To a cryptophane host molecule with high Xe affinity, we conjugated a 30mer EALA-repeat peptide that is α-helical at pH 5.5 and disordered at pH 7.5. The (129)Xe NMR chemical shift at room temperature was strongly pH-dependent (Δδ = 3.4 ppm): δ = 64.2 ppm at pH 7.5 vs δ = 67.6 ppm at pH 5.5, where Trp(peptide)-cryptophane interactions were evidenced by Trp fluorescence quenching. Using hyper-CEST NMR, we probed peptidocryptophane detection limits at low-picomolar (10(-11) M) concentration, which compares favorably to other NMR pH reporters at 10(-2)-10(-3) M. Finally, in biosensor-HeLa cell solutions, peptide-cell membrane insertion at pH 5.5 generated a 13.4 ppm downfield cryptophane-(129)Xe NMR chemical shift relative to pH 7.5 studies. This highlights new uses for (129)Xe as an ultrasensitive probe of peptide structure and function, along with potential applications for pH-dependent cell labeling in cancer diagnosis and treatment.
authors.affiliation: Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, United States.
authors.forename: Brittany A
authors.initials: BA
authors.lastname: Riggle
authors.affiliation: Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, United States.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, United States.
authors.forename: Ivan J
authors.initials: IJ
authors.lastname: Dmochowski
mesh_terms: D000595:Amino Acid Sequence; D015374:Biosensing Techniques / Q000379:methods*; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000175:diagnosis; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D010455:Peptides / Q000737:chemistry*; D011083:Polycyclic Compounds / Q000737:chemistry*; D017433:Protein Structure, Secondary; D014979:Xenon Isotopes / Q000737:chemistry*
chemical_list: D010455:Peptides; D011083:Polycyclic Compounds; D014979:Xenon Isotopes; C523242:cryptophane
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