Directly Functionalized Cucurbit[7]uril as a Biosensor for the Selective Detection of Protein Interactions by 129 Xe hyperCEST NMR
Directly Functionalized Cucurbit[7]uril as a Biosensor for the Selective Detection of Protein Interactions by 129 Xe hyperCEST NMR
复制标题
直接功能化的葫芦[7]尿素作为生物传感器，用于通过 129 Xe hyperCEST™NMR 选择性检测蛋白质相互作用
DOI：
10.1002/chem.201900610
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Pines, Alexander
中科院分区：
文献类型：
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作者：
Truxal, Ashley E.;Cao, Liping;Isaacs, Lyle;Wemmer, David E.;Pines, Alexander
超极化129磁共振成像技术向临床环境的进步表明了这种诊断成像方式的相当大的兴趣。用于129 μ m MRI的造影剂（称为生物传感器）的数量已经增长并多样化，这些造影剂对特定的生物靶点有反应。直接官能化的载氙大环化合物，例如基于隐黄素的生物传感器的大家族，对于基于定位的成像是有益的，并且在结合事件发生之前和之后提供对比。非共价官能化的构建体，如基于葫芦脲和环糊精的生物传感器，受益于CEST成像的商业可用性和最佳交换动力学。在这项工作中，我们报告了第一个直接功能化的葫芦脲用作氙生物传感器。生物素化的葫芦[7]脲（btCB 7）在与其蛋白质靶结合时产生δ=28 ppm的不寻常位移处的129 μ π ι的hyperCEST响应，具有显著的CEST对比度。 我们认为观察到的化学位移是由于btCB 7与抗生物素蛋白结合后的变形，由接近蛋白质表面引起的。构象搜索和分子动力学（MD）模拟支持这一假设。该构建体结合了两个生物传感器家族的优势，通过抗生物素蛋白缀合实现了多种生物靶标，并展示了基于功能化葫芦脲的生物传感器的优势。
Advancement of hyperpolarized129Xe MRI technology toward clinical settings demonstrates the considerable interest in this modality for diagnostic imaging. The number of contrast agents, termed biosensors, for129Xe MRI that respond to specific biological targets, has grown and diversified. Directly functionalized xenon‐carrying macrocycles, such as the large family of cryptophane‐based biosensors, are good for localization‐based imaging and provide contrast before and after binding events occur. Noncovalently functionalized constructs, such as cucurbituril‐ and cyclodextrin‐based biosensors, benefit from commercial availability and optimal exchange dynamics for CEST imaging. In this work, we report the first directly functionalized cucurbituril used as a xenon biosensor. Biotinylated cucurbit[7]uril (btCB7) gives rise to a129Xe hyperCEST response at the unusual shift ofδ=28 ppm when bound to its protein target with substantial CEST contrast. We posit that the observed chemical shift is due to the deformation of btCB7 upon binding to avidin, caused by proximity to the protein surface. Conformational searches and molecular dynamics (MD) simulations support this hypothesis. This construct combines the strengths of both families of biosensors, enables a multitude of biological targets through avidin conjugation, and demonstrates the advantages of functionalized cucurbituril‐based biosensors.