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Issue 11, 2017
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Nanomolar small-molecule detection using a genetically encoded 129Xe NMR contrast agent

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Abstract

Genetically encoded magnetic resonance imaging (MRI) contrast agents enable non-invasive detection of specific biomarkers in vivo. Here, we employed the hyper-CEST 129Xe NMR technique to quantify maltose (32 nM to 1 mM) through its modulation of conformational change and xenon exchange in maltose binding protein (MBP). Remarkably, no hyper-CEST signal was observed for MBP in the absence of maltose, making MBP an ultrasensitive “smart” contrast agent. The resonance frequency of 129Xe bound to MBP was greatly downfield-shifted (Δδ = 95 ppm) from the 129Xe(aq) peak, which facilitated detection in E. coli as well as multiplexing with TEM-1 β-lactamase. Finally, a Val to Ala mutation at the MBP–Xe binding site yielded 34% more contrast than WT, with 129Xe resonance frequency shifted 59 ppm upfield from WT. We conclude that engineered MBPs constitute a new class of genetically encoded, analyte-sensitive molecular imaging agents detectable by 129Xe NMR/MRI.

Graphical abstract: Nanomolar small-molecule detection using a genetically encoded 129Xe NMR contrast agent

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Publication details

The article was received on 17 Aug 2017, accepted on 20 Sep 2017 and first published on 20 Sep 2017


Article type: Edge Article
DOI: 10.1039/C7SC03601A
Citation: Chem. Sci., 2017,8, 7631-7636
  • Open access: Creative Commons BY-NC license
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    Nanomolar small-molecule detection using a genetically encoded 129Xe NMR contrast agent

    B. W. Roose, S. D. Zemerov and I. J. Dmochowski, Chem. Sci., 2017, 8, 7631
    DOI: 10.1039/C7SC03601A

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