Nanomolar small-molecule detection using a genetically encoded 129Xe NMR contrast agent.
Nanomolar small-molecule detection using a genetically encoded 129Xe NMR contrast agent.
Chem Sci. 2017 Nov 01;8(11):7631-7636
Authors: Roose BW, Zemerov SD, Dmochowski IJ
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 (?? = 95 ppm) from the 129Xe(aq) peak, which facilitated detection in E. coli as well as multiplexing with TEM-1 ?-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.
PMID: 29568427 [PubMed]
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