Journal of the American Chemical Society · 2010 · 83 citations · 4 references
Natural SciencesBiochemistryChemistryDiagnostic ImagingMolecular ImagingNucleic Acid ChemistryMagnetic Resonance ImagingMagnetic Resonance Imaging PhysicsMagnetic Resonance Molecular ImagingMagnetic Resonance Signal FormationMagnetic Resonance SpectroscopySpectroscopy Of BiomoleculesChemical Exchange Saturation Transfer ImagingChemical Shift AnalysisChemical Shift ImagingFrequency TransferMagnetic ResonanceMagnetic Resonance Imaging Contrast AgentsMolecular Contrast AgentsSaturation Transfer Contrast
The authors introduce FLEX, an exchange‑rate‑filtered MR method that enables detection of low‑concentration, rapidly exchanging solute protons, aiming to study dynamic nucleic acid and protein regions. FLEX uses frequency‑labeled exchange to transfer proton signals to the water resonance, preserving chemical‑shift specificity and boosting sensitivity by orders of magnitude, allowing detection of previously invisible nucleic acid and peptide protons and CEST agents. The technique successfully detects multiple rapidly exchanging protons via the water signal, achieving high sensitivity and chemical‑shift specificity, and offers a new route for developing multifrequency exchange‑based MRI contrast agents.
We report an "exchange-rate-filtered" magnetic resonance approach that allows the detection of exchangeable protons of low-concentration solutes without interference from nonexchanging protons. This indirect detection of signals of multiple rapidly exchanging protons through the water signal can be achieved while retaining chemical shift specificity and increasing the sensitivity by several orders of magnitude with respect to standard spectroscopy. This frequency-labeled exchange (FLEX) transfer principle is applied to detect previously "invisible" protons of some nucleic acids and peptides as well as rapidly exchanging protons (k > 300 s−1) in so-called chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) contrast agents. The FLEX methodology is expected to provide a practical approach for the study of highly dynamic regions of nucleic acids and proteins where amide, amino, and imino groups are rapidly moving between a closed solvent-inaccessible state and an exposed state where exchange occurs. This alternative method of labeling and detecting exchangeable protons is also expected to greatly benefit the development of new exchange-based MRI contrast agents, providing a method for multifrequency detection using frequency transfer instead of saturation transfer.
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