Artificial receptors for the recognition of phosphorylated molecules.

Artificial receptors for the recognition of phosphorylated molecules.
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人工受体识别磷酸化分子。

DOI:
10.1021/cr100242s
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发表时间:
2011-11-09
期刊:
影响因子:
62.1
通讯作者:
Anslyn, Eric V.
Anslyn, Eric V.
中科院分区:
化学1区
文献类型:
--
作者:
Hargrove, Amanda E.;Nieto, Sonia;Zhang, Tianzhi;Sessler, Jonathan L.;Anslyn, Eric V.

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磷酸阴离子是生命系统中最重要的组成部分之一。磷酸盐与杂环碱基和糖一起构成了DNA,这是生命系统的遗传元素。此外,磷酸盐离子及其衍生物在生物系统的能量储存和转导中起着关键作用。蛋白磷酸化是信号传导的关键机制,磷酸化蛋白是摄入磷酸盐的重要来源。此外,磷酸盐在工业上是药物和肥料的重要成分。来自磷酸盐和磷酸化化合物的污染是自然水源富营养化的部分原因,导致有毒藻华的危险增加。3,4磷酸也有重要的医学意义。正常情况下,过量的磷酸盐会通过肾脏排出;然而,控制肾功能衰竭患者的血磷水平是一个难题,目前还没有足够的解决方案。高磷血症,定义为异常高浓度的血清磷酸盐水平,是一种影响几乎所有血液透析患者的疾病。5,6高磷血症的不良反应包括甲状旁腺功能亢进、软组织钙化、心脏转移性钙化引起的心血管并发症,以及发病率和死亡率的增加。7À18考虑到磷酸盐在环境和生物学中的核心作用,近100年来人们一直在努力实现磷酸盐和磷酸化分子的选择性结合,这也许并不奇怪。1914年,泰勒和米勒发明了一种测定生物材料中磷含量的比色法。这种方法,现在得到了很大的改进,20À34依靠有色钼(IV)磷酸络合物来测定无机磷酸盐。这种复合物是由钼酸钠和一种强还原剂制成的,其过程通常很耗时。它还会产生有毒的金属废物,并受到干扰。磷酸化分子的其他传统检测方法涉及衍生化protocols35À44或生物识别元件,如酶,这些元件通常需要特殊处理,或者稳定性差,生产过程复杂,成本高。45À51合成(非生物)磷酸盐受体的研究旨在为生物、化学和环境重要磷酸盐的检测、提取和运输提供改进的方法。尽管已被广泛研究,磷酸化分子的敏感和选择性结合仍然是超分子化学研究的一个具有挑战性的领域。磷酸阴离子的大尺寸和高亲水性使其在基于吉布斯水化自由能的Hofmeister52选择性系列中接近底部。例如,在单碱阴离子的情况下,水合能(在括号中给出)增加
Phosphate anions are one of the most important constituents of living systems. Together with heterocyclic bases and sugars, phosphates make up DNA, the hereditary element of living systems. 1, 2 In addition, phosphate ions and their derivatives play pivotal roles in energy storage and transduction in biological systems. Protein phosphorylation is a key mechanism for signaling, and phosphorylated proteins are a significant source of ingested phosphate. Furthermore, phosphates are industrially important components of both medicinal drugs and fertilizers. Pollution from phosphate and phosphorylated compounds is in part responsible for the eutrophication of natural water sources, leading to a dangerous increase in toxic algal blooms. 3, 4 Phosphate also has important medicinal implications. Normally, excess phosphate is cleared through the kidneys; however, controlling the blood phosphate levels of patients with kidney failure is a difficult problem for which there is no adequate solution. Hyperphosphatemia, defined as an abnormally high concentration of serum phosphate levels, is a condition that affects nearly all hemodialysis patients. 5, 6 The adverse effects of hyperphosphatemia include the development of hyperparathyroidism, soft tissue calcification, cardiovascular complications resulting from the development of metastatic calcifications at the cardiac level, and increased morbidity and mortality. 7À18 Given the central role phosphate plays in the environment and in biology, it is perhaps not surprising that efforts have been made to achieve the selective binding of phosphate and phosphorylated molecules for almost 100 years. In 1914, Taylor and Miller developed a colorimetric method for the estimation of phosphorus in biological material. 19 This method, now much improved, 20À34 relies on a colored molybdenum (IV) phosphate complex to assay inorganic phosphate. This complex is produced from sodium molybdate and a strong reducing agent and involves a procedure that is often time-consuming. It also generates toxic metal waste and suffers from interference. Other traditional assays for phosphorylated molecules have involved derivatization-based protocols35À44 or biological recognition elements, such as enzymes, that often require special handling or that suffer from poor stability and complicated, costly production procedures. 45À51 The investigation of synthetic (abiotic) phosphate receptors seeks to provide improved methodologies for the detection, extraction, and transport of biologically, chemically, and environmentally important phosphates. Although it has been extensively pursued, the sensitive and selective binding of phosphorylated molecules remains a challenging area of research in supramolecular chemistry. The large size of the phosphate anion and its high hydrophilicity place it near the bottom of the Hofmeister52 selectivity series, which is based on the Gibbs free energy of hydration. In the case of monobasic anions, for instance, the hydration energies (given in parentheses) increase
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影响因子: 4.3
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DOI: 10.1039/b504931h
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影响因子: 3.2
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DOI: 10.1039/b000118j
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期刊: JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2
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Aguilar, JA;Celda, B;Tejero, R
通讯作者: Tejero, R