title: Enantiopure Cryptophane-129Xe Nuclear Magnetic Resonance Biosensors Targeting Carbonic Anhydrase.
abstract: The (+) and (-) enantiomers for a cryptophane-7-bond-linker-benzenesulfonamide biosensor (C7B) were synthesized and their chirality confirmed by electronic circular dichroism (ECD) spectroscopy. Biosensor binding to carbonic anhydrase II (CAII) was characterized for both enantiomers by hyperpolarized (hp)129Xe NMR spectroscopy. Our previous study of the racemic (+/-)C7Bbiosensor-CAII complex [Chambers, et al., J. Am. Chem. Soc. 2009,131, 563-569], identified two "bound"129Xe@C7Bpeaks by hp129Xe NMR (at 71 and 67 ppm, relative to "free" biosensor at 64 ppm), which led to the initial hypothesis that (+) and (-) enantiomers produce diastereomeric peaks when coordinated to Zn2+at the chiral CAII active site. Unexpectedly, the single enantiomers complexed with CAII also identified two "bound"129Xe@C7Bpeaks: (+) 72, 68 ppm and (-) 68, 67 ppm. These results are consistent with X-ray crystallographic evidence for benzenesulfonamide inhibitors occupying a second site near the CAII surface. As illustrated by our studies of this model protein-ligand interaction, hp129Xe NMR spectroscopy can be useful for identifying supramolecular assemblies in solution.
authors.affiliation: Department of Chemistry, University of Pennsylvania, 231 South 34 St., Philadelphia, PA 19104.
authors.forename: Olena
authors.initials: O
authors.lastname: Taratula
authors.affiliation: Department of Chemistry, University of Pennsylvania, 231 South 34 St., Philadelphia, PA 19104.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Chemistry, University of Pennsylvania, 231 South 34 St., Philadelphia, PA 19104.
authors.forename: Edward L
authors.initials: EL
authors.lastname: D'Antonio
authors.affiliation: Department of Chemistry, University of Pennsylvania, 231 South 34 St., Philadelphia, PA 19104.
authors.forename: Ivan J
authors.initials: IJ
authors.lastname: Dmochowski
keywords: 129Xe NMR spectroscopy; hyperpolarization; xenon biosensing