Deuteron Chemical Exchange Saturation Transfer for the Detection of Slow Motions in Rotating Solids.
Deuteron Chemical Exchange Saturation Transfer for the Detection of Slow Motions in Rotating Solids.
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DOI：
10.3389/fmolb.2021.705572
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发表时间：
2021
影响因子：
5
通讯作者：
Fu R
中科院分区：
文献类型：
--
作者：
Vugmeyster L;Ostrovsky D;Greenwood A;Fu R
我们利用魔角旋转(MAS)条件下的2H化学交换饱和转移(CEST)技术，论证了该方法用于研究固体慢运动的可行性。对于四极各向异性相互作用，CEST的本质是在整个光谱区域(S)对应的一系列偏移量范围内扫描所有涉及的构象状态的饱和图样，这转化为甲基的−60-+60 KHz的范围。当偏移量为MAS速率的一半和全整数时，发生旋转共振。最优MAS速率的选择取决于这样的条件：减少CEST轮廓图案中的旋转共振数量，并在MAS下保持足够大的活跃的四极相互作用，以保持对运动的敏感性。作为例子，我们将这项技术应用于众所周知的模型化合物二甲基砜，以及选择性地在A2的单个甲基基上氢化的淀粉样蛋白-β纤维，属于无序结构域。结果表明，DMS在高温下的两个旋转态之间的交换率在已知范围内，用静态2H核磁共振技术拟合的原纤态模型参数与先前获得的值符合得很好。此外，对于纤维，我们观察到在构象交换存在的情况下旋转共振的特征展宽，这为模型的选择和改进提供了暗示。这项工作为未来在MAS技术下将2H CEST扩展到小分子和蛋白质的多标记样品奠定了基础。
We utilized the 2H Chemical Exchange Saturation Transfer (CEST) technique under magic angle spinning (MAS) conditions to demonstrate the feasibility of the method for studies of slow motions in the solid state. For the quadrupolar anisotropic interaction, the essence of CEST is to scan the saturation pattern over a range of offsets corresponding to the entire spectral region(s) for all conformational states involved, which translates into a range of −60–+ 60 kHz for methyl groups. Rotary resonances occur when the offsets are at half-and full-integer of the MAS rates. The choice of the optimal MAS rate is governed by the condition to reduce the number of rotary resonances in the CEST profile patterns and retain a sufficiently large quadrupolar interaction active under MAS to maintain sensitivity to motions. As examples, we applied this technique to a well-known model compound dimethyl-sulfone (DMS) as well as amyloid-β fibrils selectively deuterated at a single methyl group of A2 belonging to the disordered domain. It is demonstrated that the obtained exchange rate between the two rotameric states of DMS at elevated temperatures fell within known ranges and the fitted model parameters for the fibrils agree well with the previously obtained value using static 2H NMR techniques. Additionally, for the fibrils we have observed characteristic broadening of rotary resonances in the presence of conformational exchange, which provides implications for model selection and refinement. This work sets the stage for future potential extensions of the 2H CEST under MAS technique to multiple-labeled samples in small molecules and proteins.