Time-sharing evolution and sensitivity enhancements in 2D HSQC-TOCSY and HSQMBC experiments

Modifications of time-shared (TS) HSQC-like experiments originally developed by Griesinger and co-workers (Sattler M, Maurer M, Schleucher J, Griesinger C. J. Biomol. NMR 1995; 5: 97) are proposed to extract different types of information from a single NMR pulse scheme. It is shown that simultaneous acquisition of 1H,13C and 1H,15N HSQC-TOCSY and HSQMBC experiments can afford experimental sensitivity enhancements of 20-40% with respect to the separate acquisition of individual 13C or 15N data. In addition, the incorporation of a number of independent editing elements can be easily used for different purposes, for instance, to assign unambiguously 1H, 13C, and 15N chemical shifts, to differentiate directly from relayed cross-peaks, or to measure simultaneously long-range proton-carbon and proton-nitrogen coupling constants. The suggested methodologies can be applied to many different classes of nitrogen-containing compounds and illustrative examples are provided for the peptide cyclosporine as a demonstration of the performance of such experiments.