Department of Chemistry and Biochemistry, University of Lethbridge, 4401 University Drive West, Lethbridge AB T1K 3M4, Canada.
Toxins (Basel). 2011 Oct;3(10):1310-31. doi: 10.3390/toxins3101310. Epub 2011 Oct 21.
The structure of T-2 toxin in the solid-state is limited to X-ray crystallographic studies, which lack sufficient resolution to provide direct evidence for hydrogen-bonding interactions. Furthermore, its solution-structure, despite extensive Nuclear Magnetic Resonance (NMR) studies, has provided little insight into its hydrogen-bonding behavior, thus far. Hydrogen-bonding interactions are often an important part of biological activity. In order to study these interactions, the structure of T-2 toxin was compared in both the solution- and solid-state using NMR Spectroscopy. It was determined that the solution- and solid-state structure differ dramatically, as indicated by differences in their carbon chemical shifts, these observations are further supported by solution proton spectral parameters and exchange behavior. The slow chemical exchange process and cross-relaxation dynamics with water observed between the hydroxyl hydrogen on C-3 and water supports the existence of a preferential hydrogen bonding interaction on the opposite side of the molecule from the epoxide ring, which is known to be essential for trichothecene toxicity. This result implies that these hydrogen-bonding interactions could play an important role in the biological function of T-2 toxin and posits towards a possible interaction for the trichothecene class of toxins and the ribosome. These findings clearly illustrate the importance of utilizing solid-state NMR for the study of biological compounds, and suggest that a more detailed study of this whole class of toxins, namely trichothecenes, should be pursued using this methodology.
T-2 毒素的固态结构仅限于 X 射线晶体学研究，其分辨率不足以提供氢键相互作用的直接证据。此外，尽管进行了广泛的核磁共振（NMR）研究，但迄今为止，其溶液结构几乎没有提供对氢键行为的深入了解。氢键相互作用通常是生物活性的重要组成部分。为了研究这些相互作用，使用 NMR 光谱法比较了 T-2 毒素在溶液和固态中的结构。结果表明，溶液和固态结构有很大的不同，这反映在它们的碳化学位移差异上，这些观察结果进一步得到了溶液质子光谱参数和交换行为的支持。在 C-3 上的羟基氢与水之间观察到的缓慢化学交换过程和交叉弛豫动力学支持了在分子的环氧环对面存在优先氢键相互作用的存在，这对于三噻嗪毒性是必不可少的。这一结果意味着这些氢键相互作用可能在 T-2 毒素的生物功能中发挥重要作用，并暗示三噻嗪类毒素和核糖体之间可能存在相互作用。这些发现清楚地说明了利用固态 NMR 研究生物化合物的重要性，并表明应该使用这种方法对整个三噻嗪类毒素进行更详细的研究。
