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Title: Programming A Molecular Relay for Ultrasensitive Biodetection through 129 Xe NMR

Journal Article · · Angewandte Chemie (International Edition)

We reported a supramolecular strategy for detecting specific proteins in complex media by using hyperpolarized 129Xe NMR. A cucurbit[6]uril (CB[6])-based molecular relay was programmed for three sequential equilibrium conditions by designing a two-faced guest (TFG) that initially binds CB[6] and blocks the CB[6]–Xe interaction. Moreover, the protein analyte recruits the TFG and frees CB[6] for Xe binding. TFGs containing CB[6]- and carbonic anhydrase II (CAII)-binding domains were synthesized in one or two steps. X-ray crystallography confirmed TFG binding to Zn2+ in the deep CAII active-site cleft, which precludes simultaneous CB[6] binding. The molecular relay was reprogrammed to detect avidin by using a different TFG. Finally, Xe binding by CB[6] was detected in buffer and in E. coli cultures expressing CAII through ultrasensitive 129Xe NMR spectroscopy.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
USDOE; National Institutes of Health (NIH)
Grant/Contract Number:
R01-GM097478; LC130824; S10-DO016260
OSTI ID:
1260842
Journal Information:
Angewandte Chemie (International Edition), Vol. 55, Issue 5; ISSN 1433-7851
Publisher:
WileyCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 23 works
Citation information provided by
Web of Science

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Cited By (16)

Rotaxane Probes for the Detection of Hydrogen Peroxide by 129 Xe HyperCEST NMR Spectroscopy journal June 2019
A Genetically Encoded β-Lactamase Reporter for Ultrasensitive 129 Xe NMR in Mammalian Cells journal June 2016
Rotaxane Probes for the Detection of Hydrogen Peroxide by 129 Xe HyperCEST NMR Spectroscopy journal July 2019
Directly Functionalized Cucurbit[7]uril as a Biosensor for the Selective Detection of Protein Interactions by 129 Xe hyperCEST NMR journal February 2019
Quantitative Assessment of Xenon Exchange Kinetics with Cucurbit[6]uril in Physiological Saline journal June 2018
A Structural Basis for 129 Xe Hyper-CEST Signal in TEM-1 β-Lactamase journal September 2018
Thermodynamic, kinetic, and structural parameterization of human carbonic anhydrase interactions toward enhanced inhibitor design journal January 2018
In vivo detection of cucurbit[6]uril, a hyperpolarized xenon contrast agent for a xenon magnetic resonance imaging biosensor journal January 2017
129 Xe NMR-based sensors: biological applications and recent methods journal January 2017
An intracellular diamine oxidase triggered hyperpolarized 129 Xe magnetic resonance biosensor journal January 2018
A supramolecular five-component relay switch that exposes the mechanistic competition of dissociative versus associative binding to cucurbiturils by ratiometric fluorescence monitoring journal January 2019
A Genetically Encoded β-Lactamase Reporter for Ultrasensitive 129 Xe NMR in Mammalian Cells journal June 2016
Thermodynamic, kinetic, and structural parameterization of human carbonic anhydrase interactions toward enhanced inhibitor design text January 2018
An Expanded Palette of Xenon-129 NMR Biosensors journal September 2016
Cyclodextrin-Based Pseudorotaxanes: Easily Conjugatable Scaffolds for Synthesizing Hyperpolarized Xenon-129 Magnetic Resonance Imaging Agents journal January 2018
Probing Reversible Guest Binding with Hyperpolarized 129Xe-NMR: Characteristics and Applications for Cucurbit[n]urils journal February 2020