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Chapter 15

Cryptophane-Based 129Xe NMR Biosensors

To expand the capabilities of hyperpolarized (HP) 129Xe NMR for sensitive biodetection, a cryptophane host molecule can be specifically targeted to analytes of interest. Water-soluble cryptophanes have been generated with increased xenon affinity (KD=20–30 µM at rt) and 129Xe NMR chemical shifts over a broad (∼300 ppm) spectral window. In particular, trifunctionalized cryptophanes have enabled conjugation of a variety of targeting and solubilizing ligands, and provided routes to enantiopure material. Cryptophane was engineered to bind carbonic anhydrase (CA) II with nanomolar affinity, by attaching a benzenesulfonamide ligand and two water-solubilizing moieties; Zn2+ coordination in the active-site channel was confirmed by X-ray crystallography. Using xenon biosensors tailored for CA, progress has been made in manipulating and better resolving the 129Xe NMR chemical shift, as required for multiplexing studies. In one example, HP 129Xe NMR chemical shift changes as large as 7.5 ppm were observed upon CAII binding. Finally, chemical exchange saturation transfer (CEST) NMR has enabled low-picomolar cryptophane detection, which creates unique biosensing opportunities.

Publication details

Print publication date
14 Apr 2015
Copyright year
2015
Print ISBN
978-1-84973-889-7
PDF eISBN
978-1-78262-837-8
ePub eISBN
978-1-78262-488-2

From the book series:
New Developments in NMR