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用于高信号 fMRI 造影剂模块化设计的无规卷曲氟代肽的合成。

Synthesis of Intrinsically Disordered Fluorinated Peptides for Modular Design of High-Signal F MRI Agents.

机构信息

Department of Chemistry, University of Minnesota - Twin Cities, 207 Pleasant St. SE, Minneapolis, MN, 55455, USA.

Department of Radiology, Center for Magnetic Resonance Research, University of Minnesota - Twin Cities, 2021 6thSt. SE, Minneapolis, MN, 55455, USA.

出版信息

Angew Chem Int Ed Engl. 2017 Jun 1;56(23):6440-6444. doi: 10.1002/anie.201700426. Epub 2017 May 4.

Abstract

F MRI is valuable for in vivo imaging due to the only trace amounts of fluorine in biological systems. Because of the low sensitivity of MRI however, designing new fluorochemicals remains a significant challenge for achieving sufficient F signal. Here, we describe a new class of high-signal, water-soluble fluorochemicals as F MRI imaging agents. A polyamide backbone is used for tuning the proteolytic stability to avoid retention within the body, which is a limitation of current state-of-the-art perfluorochemicals. We show that unstructured peptides containing alternating N-ϵ-trifluoroacetyllysine and lysine provide a degenerate F NMR signal. F MRI phantom images provide sufficient contrast at micromolar concentrations, showing promise for eventual clinical applications. Finally, the degenerate high signal characteristics were retained when conjugated to a large protein, indicating potential for in vivo targeting applications, including molecular imaging and cell tracking.

摘要

由于生物系统中氟的含量极少,因此 fMRI 在体内成像是很有价值的。然而,由于 MRI 的灵敏度较低,因此设计新的氟化学物质仍然是实现足够 F 信号的重大挑战。在这里,我们描述了一类新的高信号、水溶性氟化学物质,它们可用作 F MRI 成像剂。采用聚酰胺骨架来调整蛋白水解稳定性,以避免在体内保留,这是当前最先进的全氟化学物质的一个局限性。我们表明,含有交替的 N-ε-三氟乙酰赖氨酸和赖氨酸的无规多肽提供了退化的 F NMR 信号。F MRI 体模图像在微摩尔浓度下提供了足够的对比度,显示出最终临床应用的前景。最后,当与大蛋白结合时,退化的高信号特性得以保留,表明有可能用于体内靶向应用,包括分子成像和细胞跟踪。

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