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. 2016 Jan 26;55(5):1733-6.
doi: 10.1002/anie.201508990. Epub 2015 Dec 21.

Programming A Molecular Relay for Ultrasensitive Biodetection through (129)Xe NMR

Yanfei Wang  1 , Benjamin W Roose  1 , John P Philbin  1 , Jordan L Doman  1 , Ivan J Dmochowski  2
Affiliations

Programming A Molecular Relay for Ultrasensitive Biodetection through (129)Xe NMR

Yanfei Wang et al. Angew Chem Int Ed Engl. .

Erratum in

Abstract

A supramolecular strategy for detecting specific proteins in complex media by using hyperpolarized (129) Xe NMR is reported. 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. 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 Zn(2+) 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 (129) Xe NMR spectroscopy.

Keywords: NMR spectroscopy; bioinorganic chemistry; biosensors; host-guest systems; molecular recognition.

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Figures

Figure 1
Figure 1
X-ray crystal structure of TFG 3 bound to CAII. (Left) Simulated annealing omit map (contoured at 3σ) shows 3 bound to Zn2+ (green sphere) in the active site of CAII. Interatomic distances (solid purple lines) are labeled in Å. Water molecules are omitted for clarity. (Right) CAII active-site channel is represented as a surface model (hydrophobes in red; hydrophilic residues in white).
Figure 2
Figure 2
Comparison of CAII esterase activity with different TFGs and CB[6]-TFG complexes monitored using pNPA as substrate. All assays were performed after 20 min incubation. Standard errors were determined from three or more replicates for each condition.
Figure 3
Figure 3
Frequency-dependent 129Xe NMR saturation spectra in pH 7.2 PBS at 300 K showed CAII detection via CB[6]-4 molecular relay.
Figure 4
Figure 4
Frequency-dependent 129Xe NMR saturation spectra in pH 7.2 PBS at 300 K showed avidin detection via CB[6]-pAB molecular relay.
Figure 5
Figure 5
Frequency-dependent 129Xe NMR saturation spectra showed CAII detection via CB[6]-4 relay in bacterial lysate (OD600nm = 2) at 300 K.
Scheme 1
Scheme 1
Molecular relay produces 129Xe NMR signal upon analyte detection.
See this image and copyright information in PMC

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