Indirect detection of labile solute proton spectra via the water signal using frequency-labeled exchange (FLEX) transfer.

ABSTRACT: 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.

SUBMITTER: Friedman JI 

PROVIDER: S-EPMC2822835 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature