Extending the Sensitivity of CEST NMR Spectroscopy to Micro‐to‐Millisecond Dynamics in Nucleic Acids Using High‐Power Radio‐Frequency Fields

• Published in: Angewandte Chemie International Edition Vol. 59; no. 28; pp. 11262 - 11266
• Main Authors: Rangadurai, Atul, Shi, Honglue, Al‐Hashimi, Hashim M.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 06.07.2020
• Edition: International ed. in English
• Subjects: Biomolecules; biophysics; Catalysis; chemical exchange saturation transfer; Data acquisition; DNA - chemistry; DNA structures; Irradiation; Limit of Detection; Magnetic resonance spectroscopy; Magnetic Resonance Spectroscopy - methods; Motion; NMR; NMR spectroscopy; Nuclear magnetic resonance; Nucleic acids; Radiation; Radio Waves; Sensitivity; structural dynamics; Time; nucleic acids; structural dynamics; biophysics; DNA structures; chemical exchange saturation transfer
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202000493

Biomolecules undergo motions on the micro‐to‐millisecond timescale to adopt low‐populated transient states that play important roles in folding, recognition, and catalysis. NMR techniques, such as Carr–Purcell–Meiboom–Gill (CPMG), chemical exchange saturation transfer (CEST), and R1ρ are the most commonly used methods for characterizing such transitions at atomic resolution under solution conditions. CPMG and CEST are most effective at characterizing motions on the millisecond timescale. While some implementations of the R1ρ experiment are more broadly sensitive to motions on the micro‐to‐millisecond timescale, they entail the use of selective irradiation schemes and inefficient 1D data acquisition methods. Herein, we show that high‐power radio‐frequency fields can be used in CEST experiments to extend the sensitivity to faster motions on the micro‐to‐millisecond timescale. Given the ease of implementing high‐power fields in CEST, this should make it easier to characterize micro‐to‐millisecond dynamics in biomolecules. I′ve got the power: High‐power radio‐frequency fields extend the sensitivity of chemical exchange saturation transfer (CEST) NMR spectroscopy to enable the detection of conformational exchange on the micro‐to‐millisecond timescale. This is applied to the detection of nucleic‐acid dynamics.