Systematic Study of Protein Detection Mechanism of Self-Assembling 19F NMR/MRI Nanoprobes toward Rational Design and Improved Sensitivity
Systematic Study of Protein Detection Mechanism of Self-Assembling 19F NMR/MRI Nanoprobes toward Rational Design and Improved Sensitivity
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DOI：
10.1021/ja203996c
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发表时间：
2011-08-03
影响因子：
15
通讯作者：
Hamachi, Itaru
中科院分区：
文献类型：
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作者：
Takaoka, Yousuke;Kiminami, Keishi;Hamachi, Itaru
F-19核磁共振/磁共振探针具有灵敏度高、无背景信号等优点，有望成为生物活性物质选择性检测的有力工具。我们最近报道了一种独特的超分子策略，使用蛋白质配体拴系的自组装F-19探针进行特异性蛋白质检测。该方法基于纳米探针的分解驱动的拆卸，其诱导了F-19 NMR/MRI的清晰开启信号。在本研究中，我们进行了系统的调查之间的关系的结构和性质的探针，以阐明这种开启的F-19 NMR传感的详细机制。新合成的F-19探针对靶蛋白表现出三种不同的响应行为：关/开、始终开启和始终关闭模式。我们清楚地表明，蛋白质响应的这些差异可以通过探针聚集体的稳定性差异来解释，并且聚集体的“中等稳定性”在蛋白质检测中产生理想的开启响应。我们还通过改变探针的疏水性/亲水性平衡成功地控制了聚集体的稳定性。对检测机制的详细了解使我们能够合理设计具有更高灵敏度的开启F-19 NMR探针，从而在F-19 MRI中为靶蛋白提供更高的图像强度。
F-19 NMR/MRI probe is expected to be a powerful tool for selective sensing of biologically active agents owing to its high sensitivity and no background signals in live bodies. We have recently reported a unique supramolecular strategy for specific protein detection using a protein ligand-tethered self-assembling F-19 probe. This method is based on a recognition-driven disassembly of the nanoprobes, which induced a clear turn-on signal of F-19 NMR/MRI. In the present study, we conducted a systematic investigation of the relationship between structure and properties of the probe to elucidate the mechanism of this turn-on F-19 NMR sensing in detail. Newly synthesized F-19 probes showed three distinct behaviors in response to the target protein: off/on, always-on, and always-off modes. We clearly demonstrated that these differences in protein response could be explained by differences in the stability of the probe aggregates and that "moderate stability" of the aggregates produced an ideal turn-on response in protein detection. We also successfully controlled the aggregate stability by changing the hydrophobicity/hydrophilicity balance of the probes. The detailed understanding of the detection mechanism allowed us to rationally design a turn-on F-19 NMR probe with improved sensitivity, giving a higher image intensity for the target protein in F-19 MRI.