A Genetically Encoded β-Lactamase Reporter for Ultrasensitive (129) Xe NMR in Mammalian Cells.
Yanfei WangBenjamin W RooseEugene J PalovcakVincenzo CarnevaleIvan J DmochowskiPublished in: Angewandte Chemie (International ed. in English) (2016)
Molecular imaging holds considerable promise for elucidating biological processes in normal physiology as well as disease states, but requires noninvasive methods for identifying analytes at sub-micromolar concentrations. Particularly useful are genetically encoded, single-protein reporters that harness the power of molecular biology to visualize specific molecular processes, but such reporters have been conspicuously lacking for in vivo magnetic resonance imaging (MRI). Herein, we report TEM-1 β-lactamase (bla) as a single-protein reporter for hyperpolarized (HP) (129) Xe NMR, with significant saturation contrast at 0.1 μm. Xenon chemical exchange saturation transfer (CEST) interactions with the primary allosteric site in bla give rise to a unique saturation peak at 255 ppm, well removed (≈60 ppm downfield) from the (129) Xe-H2 O peak. Useful saturation contrast was also observed for bla expressed in bacterial cells and mammalian cells.
Keyphrases
- klebsiella pneumoniae
- magnetic resonance
- magnetic resonance imaging
- contrast enhanced
- escherichia coli
- multidrug resistant
- high resolution
- crispr cas
- induced apoptosis
- protein protein
- computed tomography
- gram negative
- small molecule
- gold nanoparticles
- solid state
- diffusion weighted imaging
- single molecule
- quantum dots
- deep learning
- oxidative stress
- endoplasmic reticulum stress
- mass spectrometry
- artificial intelligence
- electron transfer