Category Archives: CEST

Sensitivity-enhanced detection of non-labile proton and carbon NMR spectra on water resonances #DNPNMR

Novakovic, M., et al., Sensitivity-enhanced detection of non-labile proton and carbon NMR spectra on water resonances. Phys. Chem. Chem. Phys., 2017. 20(1): p. 56-62.

https://www.ncbi.nlm.nih.gov/pubmed/29171604

Chemical exchange saturation transfer (CEST) experiments enhance the NMR signals of labile protons by continuously transferring these protons’ saturation to an abundant solvent pool like water. The present study expands these principles by fusing into these experiments homonuclear isotropic mixing sequences, enabling the water-enhanced detection of non-exchangeable species. Further opportunities are opened by the addition of coupling-mediated heteronuclear polarization transfers, which then impose on the water resonance a saturation stemming from non-labile heteronuclear species like (13)C. To multiplex the ensuing experiments, these relayed approaches are combined with time-domain schemes involving multiple Ramsey-labeling experiments imparting the frequencies of the non-labile sites on the water resonance, via chemical exchange. (13)C and (1)H NMR spectra were detected in this fashion with about two-fold SNR amplification vis-a-vis conventionally detected spectroscopies. When combined with non-uniform sampling principles, this methodology thus becomes a sensitive alternative to detect non-exchangeable species in biomolecules. Still, multiple parameters including the scalar couplings and solvent exchange rates, will affect the efficiency and consequently the practicality of the overall experiment.

Rotaxane probes for protease detection by 129Xe hyperCEST NMR

Slack, C.C., et al., Rotaxane probes for protease detection by 129Xe hyperCEST NMR. Chem Commun (Camb), 2017. 53(6): p. 1076-1079.

https://www.ncbi.nlm.nih.gov/pubmed/28044166

We report a CB6 rotaxane for the 129Xe hyperCEST NMR detection of matrix metalloprotease 2 (MMP-2) activity. MMP-2 is overexpressed in cancer tissue, and hence is a cancer marker. A peptide containing an MMP-2 recognition sequence was incorporated into the rotaxane, synthesized via CB6-promoted click chemistry. Upon cleavage of the rotaxane by MMP-2, CB6 became accessible for 129Xe@CB6 interactions, leading to protease-responsive hyperCEST activation.

Rotaxane-mediated suppression and activation of cucurbit[6]uril for molecular detection by (129)Xe hyperCEST NMR

Finbloom, J.A., et al., Rotaxane-mediated suppression and activation of cucurbit[6]uril for molecular detection by (129)Xe hyperCEST NMR. Chem Commun (Camb), 2016. 52(15): p. 3119-22.

http://www.ncbi.nlm.nih.gov/pubmed/26795714

We report a method for blocking interactions between (129)Xe and cucurbit[6]uril (CB6) until activation by a specific chemical event. We synthesized a CB6-rotaxane that allowed no (129)Xe interaction with the CB6 macrocycle component until a cleavage event released the CB6, which then produced a (129)Xe@CB6 NMR signal. This contrast-upon-activation (129)Xe NMR platform allows for modular synthesis and can be expanded to applications in detection and disease imaging.

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