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.
Assessment of a Heuristic Model for Characterization of Magnetic Nanoparticles as Contrast Agent in MRI
From The DNP-NMR Blog:
Assessment of a Heuristic Model for Characterization of Magnetic Nanoparticles as Contrast Agent in MRI
Félix-González, N., et al., Assessment of a Heuristic Model for Characterization of Magnetic Nanoparticles as Contrast Agent in MRI. Concepts in Magnetic Resonance Part A, 2015. 44A(5): p. 279-286.
http://dx.doi.org/10.1002/cmr.a.21361
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08-03-2016 05:31 PM
[NMR paper] A Genetically Encoded ?-Lactamase Reporter for Ultrasensitive (129) Xe NMR in Mammalian Cells.
A Genetically Encoded ?-Lactamase Reporter for Ultrasensitive (129) Xe NMR in Mammalian Cells.
Related Articles A Genetically Encoded ?-Lactamase Reporter for Ultrasensitive (129) Xe NMR in Mammalian Cells.
Angew Chem Int Ed Engl. 2016 Jun 15;
Authors: Wang Y, Roose BW, Palovcak EJ, Carnevale V, Dmochowski IJ
Abstract
Molecular imaging holds considerable promise for elucidating biological processes in normal physiology as well as disease states, but requires noninvasive methods for identifying analytes at sub-micromolar...
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06-16-2016 12:06 PM
Cucurbit[6]uril is an ultrasensitive (129)Xe NMR contrast agent
From The DNP-NMR Blog:
Cucurbituril is an ultrasensitive (129)Xe NMR contrast agent
Wang, Y. and I.J. Dmochowski, Cucurbituril is an ultrasensitive (129)Xe NMR contrast agent. Chem Commun (Camb), 2015. 51(43): p. 8982-5.
http://www.ncbi.nlm.nih.gov/pubmed/25929681
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06-11-2015 05:15 AM
[NMR paper] Development of an antibody-based, modular biosensor for 129Xe NMR molecular imaging of cells at nanomolar concentrations.
Development of an antibody-based, modular biosensor for 129Xe NMR molecular imaging of cells at nanomolar concentrations.
Development of an antibody-based, modular biosensor for 129Xe NMR molecular imaging of cells at nanomolar concentrations.
Proc Natl Acad Sci U S A. 2014 Jul 28;
Authors: Rose HM, Witte C, Rossella F, Klippel S, Freund C, Schröder L
Abstract
Magnetic resonance imaging (MRI) is seriously limited when aiming for visualization of targeted contrast agents. Images are reconstructed from the weak diamagnetic...
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07-30-2014 10:22 AM
[NMR paper] A Genetically Encoded 19 F NMR Probe for Tyrosine Phosphorylation.
A Genetically Encoded 19 F NMR Probe for Tyrosine Phosphorylation.
A Genetically Encoded 19 F NMR Probe for Tyrosine Phosphorylation.
Angew Chem Int Ed Engl. 2013 Feb 28;
Authors: Li F, Shi P, Li J, Yang F, Wang T, Zhang W, Gao F, Ding W, Li D, Li J, Xiong Y, Sun J, Gong W, Tian C, Wang J
Abstract
Simple and selective: Tyrosine phosphorylation is a pivotal post-translational modification which regulates the enzymatic activity, protein conformation, and protein-protein interactions. The highly efficient genetic incorporation of...
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03-02-2013 11:45 AM
[NMR paper] NMR Methods for Detection of Small Molecule Binding to RGS4.
NMR Methods for Detection of Small Molecule Binding to RGS4.
Related Articles NMR Methods for Detection of Small Molecule Binding to RGS4.
Methods Enzymol. 2013;522:133-52
Authors: Storaska AJ, Neubig RR
Abstract
The duration and amplitude of G-protein-coupled receptor (GPCR) signaling is controlled by regulator of G-protein signaling (RGS) proteins. The 20 RGS family members act as GTPase accelerating proteins through their interaction with the G? subunit of the G??? heterotrimer. Their influence over GPCR signaling has attracted many to...
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02-05-2013 09:51 PM
Generation of Pseudocontact Shifts in Protein NMR Spectra with a Genetically Encoded Cobalt(II)-Binding Amino Acid.
Generation of Pseudocontact Shifts in Protein NMR Spectra with a Genetically Encoded Cobalt(II)-Binding Amino Acid.
Generation of Pseudocontact Shifts in Protein NMR Spectra with a Genetically Encoded Cobalt(II)-Binding Amino Acid.
Angew Chem Int Ed Engl. 2011 Jan 17;50(3):692-4
Authors: Nguyen TH, Ozawa K, Stanton-Cook M, Barrow R, Huber T, Otting G
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01-13-2011 12:00 PM
Generation of Pseudocontact Shifts in Protein NMR Spectra with a Genetically Encoded
Generation of Pseudocontact Shifts in Protein NMR Spectra with a Genetically Encoded Cobalt(II)-Binding Amino Acid.
Related Articles Generation of Pseudocontact Shifts in Protein NMR Spectra with a Genetically Encoded Cobalt(II)-Binding Amino Acid.
Angew Chem Int Ed Engl. 2010 Nov 25;
Authors: Nguyen TH, Ozawa K, Stanton-Cook M, Barrow R, Huber T, Otting G
Nanomolar small-molecule detection using a genetically encoded 129Xe NMR contrast agent.
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