[NMR paper] A "Smart" ¹²?Xe NMR Biosensor for pH-Dependent Cell Labeling.

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A "Smart" ¹²?Xe NMR Biosensor for pH-Dependent Cell Labeling.

Related Articles A "Smart" ¹²?Xe NMR Biosensor for pH-Dependent Cell Labeling.

J Am Chem Soc. 2015 Apr 29;137(16):5542-8

Authors: Riggle BA, Wang Y, Dmochowski IJ

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 ?-helical at pH 5.5 and disordered at pH 7.5. The (129)Xe NMR chemical shift at room temperature was strongly pH-dependent (?? = 3.4 ppm): ? = 64.2 ppm at pH 7.5 vs ? = 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.


PMID: 25848822 [PubMed - indexed for MEDLINE]



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