Sensitivity and Resolution Enhanced Solid-State NMR for Paramagnetic Systems and Biomolecules under Very Fast Magic Angle Spinning
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AbstractRecent research in fast magic angle spinning (MAS) methods has drastically improved the resolution and sensitivity of NMR spectroscopy of biomolecules and materials in solids. In this Account, we summarize recent and ongoing developments in this area by presenting (13)C and (1)H solid-state NMR (SSNMR) studies on paramagnetic systems and biomolecules under fast MAS from our laboratories. First, we describe how very fast MAS (VFMAS) at the spinning speed of at least 20 kHz allows us to overcome major difficulties in (1)H and (13)C high-resolution SSNMR of paramagnetic systems. As a result, we can enhance both sensitivity and resolution by up to a few orders of magnitude. Using fast recycling (∼ms/scan) with short (1)H T1 values, we can perform (1)H SSNMR microanalysis of paramagnetic systems on the microgram scale with greatly improved sensitivity over that observed for diamagnetic systems. Second, we discuss how VFMAS at a spinning speed greater than ∼40 kHz can enhance the sensitivity and resolution of (13)C biomolecular SSNMR measurements. Low-power (1)H decoupling schemes under VFMAS offer excellent spectral resolution for (13)C SSNMR by nominal (1)H RF irradiation at ∼10 kHz. By combining the VFMAS approach with enhanced (1)H T1 relaxation by paramagnetic doping, we can achieve extremely fast recycling in modern biomolecular SSNMR experiments. Experiments with (13)C-labeled ubiquitin doped with 10 mM Cu-EDTA demonstrate how effectively this new approach, called paramagnetic assisted condensed data collection (PACC), enhances the sensitivity. Lastly, we examine (13)C SSNMR measurements for biomolecules under faster MAS at a higher field. Our preliminary (13)C SSNMR data of Aβ amyloid fibrils and GB1 microcrystals acquired at (1)H NMR frequencies of 750-800 MHz suggest that the combined use of the PACC approach and ultrahigh fields could allow for routine multidimensional SSNMR analyses of proteins at the 50-200 nmol level. Also, we briefly discuss the prospects for studying bimolecules using (13)C SSNMR under ultrafast MAS at the spinning speed of ∼100 kHz.
CitationParthasarathy S, Nishiyama Y, Ishii Y (2013) Sensitivity and Resolution Enhanced Solid-State NMR for Paramagnetic Systems and Biomolecules under Very Fast Magic Angle Spinning. Acc Chem Res 46: 2127–2135. Available: http://dx.doi.org/10.1021/ar4000482.
SponsorsThe development of novel SSNMR approaches was supported primarily by the NSF (CHE 0449952, CHE 957793). Structural studies of the amyloid fibrils were supported mainly by the NIH (9R01 GM098033) and in part by the Alzheimer’s Association (IIRG; 08-91256) and Dreyfus Foundation Teacher-Scholar Award. The instrumentation of the 750 MHz SSNMR was supported by the NIH (1S10 RR025105). We thank the JEOL Resonance for making the prototype 1-mm and 0.75-mm MAS probes available for this study. In particular, we thank Drs. Yuki Endo and Takahiro Nemoto at the JEOL Resonance for their excellent design works. We are grateful to Dr. Jochem Struppe for his advice on pulse sequences on the Bruker Avance spectrometers and Dr. Kazuo Yamauchi at the King Abdullah University of Science and Technology for prompting us to be involved in the 1 mm probe project. We also thank Dr. Fei Long and Mr. Isamu Matsuda for providing the GB1 sample and Dr. William Tay for useful comments about this manuscript. Y.I. is grateful to the late Prof. Ivano Bertini for his encouragements in the course of our studies on paramagnetic SSNMR of materials and biomolecules.
PublisherAmerican Chemical Society (ACS)
JournalAccounts of Chemical Research
PubMed Central IDPMC3778062