Environment-Sensitive Fluorescent Turn-On Probes Targeting Hydrophobic Ligand-Binding Domains for Selective Protein Detection
Environment-Sensitive Fluorescent Turn-On Probes Targeting Hydrophobic Ligand-Binding Domains for Selective Protein Detection
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DOI：
10.1002/anie.201302884
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发表时间：
2013-07-29
影响因子：
16.6
通讯作者：
Tan, Kui-Thong
中科院分区：
文献类型：
--
作者：
Zhuang, Yu-De;Chiang, Po-Yi;Tan, Kui-Thong
蛋白质特异性检测或成像在医学诊断中检测蛋白质生物标志物以及在生物学中研究细胞过程是重要的。可以检测特定蛋白质的小分子荧光开启探针特别有价值，因为它们允许敏感、简单和具有高信号与背景比的特异性检测目前大多数小分子荧光开启探针被设计用于监测酶的活性，例如糖苷酶、蛋白酶、内酰胺酶和激酶通常，它们的荧光开启机制是基于与化学探针的酶促反应，将非荧光底物转化为荧光产物。另一方面，非酶蛋白荧光探针的设计仍然是一个具有挑战性的任务。目前，已经报道了几种荧光开启策略，如发卡肽信标、[3]适体、[4]超分子方法、[5]聚合物共轭纳米颗粒、[6]和配体定向亲和标记[7]等，可以通过非酶反应检测蛋白质。荧光信号可以通过电荷-电荷相互作用、亲和标记或识别特定肽序列来识别靶蛋白。尽管这些荧光探针采用新颖的策略来检测非酶蛋白，但它们要么选择性低，要么荧光开启比小，要么仅限于检测细胞表面的蛋白质。因此，开发一种更通用的策略来产生蛋白质特异性荧光开启探针是必要的。
Protein-specific detection or imaging is important in medical diagnosis to detect protein biomarkers, as well as in biology to investigate cellular processes. Small-molecule fluorescent turn-on probes that can detect specific proteins are particularly valuable as they allow for sensitive, simple, and specific detection with high signal-to-background ratios.[1] Currently most of the small-molecule fluorescent turn-on probes are designed for monitoring enzyme activities, for example, glycosidases, proteases, lactamases, and kinases.[2] Typically, their fluorescence turn-on mechanism is based on an enzymatic reaction with the chemical probes to convert a nonfluorescent substrate into a fluorescent product. On the other hand, the design of fluorescence probes for non-enzymatic proteins remains a challenging task. Currently, several fluorescence turn-on strategies such as hairpin peptide beacons,[3] aptamers,[4] supramolecular approaches,[5] polymer-conjugated nanoparticles,[6] and ligand-directed affinity labeling [7] have been reported to detect proteins through nonenzymatic reactions. Fluorescence signals can be turned-on upon recognition of the target proteins through charge–charge interaction, affinity labeling, or recognition of a specific peptide sequence. Although these fluorescent probes use novel strategies to detect non-enzymatic proteins, nevertheless, they suffer from either low selectivity and small fluorescent turn-on ratios, or are limited to sensing proteins on the cell surface. Thus, the development of a more general strategy to generate protein-specific fluorescent turn-on probes is necessary.