Cation-π Lights Up "Halo".

Cation-π Lights Up "Halo".
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DOI:
10.1021/acs.biochem.7b00702
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发表时间:
2017-10-10
期刊:
影响因子:
2.9
通讯作者:
Gao J
Gao J
中科院分区:
生物学3区
文献类型:
--
作者:
Gao J

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自20世纪90年代多尔蒂提出阳离子−π相互作用以来,它的重要性在化学和生物学的各个方面得到了广泛的认识。例如,多尔蒂自己的工作清楚地表明了阳离子−π相互作用在神经传递中的重要性,阳离子神经递质(如乙酰胆碱)由带有芳香盒的细胞表面受体识别。甲基化的组蛋白读取器以及选择性结合哺乳动物脂类的细菌磷脂酶也有类似的机制被描述。此外,阳离子−π相互作用也被报道通过稳定阳离子过渡态来促进催化。张和他的同事在最近发表在《生物化学》上的一篇论文中揭示了阳离子−π相互作用的另一个令人兴奋的应用,即创建荧光荧光团。2在一片沼泽中对目标分子进行荧光标记在生物学研究中是非常可取的。更好的是,诱导强烈荧光增强的选择性标记反应将使活细胞和生物体中的靶标直接可视化并有可能量化。理想情况下,标记反应应该是快速和高度特异的,标记试剂是非荧光的,并在与目标分子连接时获得荧光。最近的化学生物学研究已经朝着这些目标取得了长足的进步。可以通过引入识别元件来实现对目标蛋白质的特异性,该识别元件可以是非天然氨基酸或自我标记的蛋白质标签。3在这些识别元件中,自标记蛋白质标签(SNAP、CLIP和HaloTag)具有反应快、底物范围广、不需要非天然氨基酸等优点。令人兴奋的是,基于HaloTag的标记最近被制成了荧光标记。自约翰森和他的同事最初的报告以来
Since the introduction of cation− π interaction by Dougherty in the 1990s, 1 its significance has been recognized in various aspects of chemistry and biology. For example, Dougherty’s own work has clearly shown the importance of the cation− π interaction in neurotransmission, where cationic neurotransmitters (eg, acetylcholine) are recognized by cell surface receptors with an aromatic box. Similar mechanisms have been described for readers of methylated histone proteins as well as bacterial phospholipases that selectively bind mammalian lipids. Furthermore, cation− π interaction has also been reported to facilitate catalysis by stabilizing cationic transition states. Writing in a recent paper in Biochemistry, Zhang and co-workers revealed yet another exciting application of cation− π interaction, that is, the creation of fluorogenic fluorophores. 2Fluorescent labeling of a target molecule in a swamp of others is highly desirable for biological research. Even better, selective labeling reactions that induce strong fluorescence increases would allow direct visualization and potentially quantification of the target in live cells and organisms. Ideally, a labeling reaction should be fast and highly specific, with the labeling reagent being nonfluorescent and gaining fluorescence upon conjugation to the target molecule. Recent research in chemical biology has made great strides toward these goals. Specificity toward a target protein can be achieved by introducing a recognition element, which could be an unnatural amino acid or a self-labeling protein tag. 3 Among these recognition elements, the self-labeling protein tags (SNAP, CLIP, and HaloTag) enjoy the benefit of fast reaction, a broad substrate scope, and no need for unnatural amino acids. Excitingly, HaloTag-based labeling has recently been made fluorogenic. Since the initial report by Johnsson and co-workers
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DOI: 10.1126/science.271.5246.163
发表时间: 1996-01-12
期刊: SCIENCE
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