Recognition of Solution Structures of Peptides by Molecularly Imprinted Cyclodextrin Polymers
Recognition of Solution Structures of Peptides by Molecularly Imprinted Cyclodextrin Polymers
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DOI：
10.1021/ma070348f
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发表时间：
2007-04
期刊：
影响因子：
5.5
通讯作者：
Shi-Hui Song;K. Shirasaka;Mami Katayama;Suguru Nagaoka;Shinji Yoshihara;Tomo Osawa;J. Sumaoka;H. Asanuma;M. Komiyama
中科院分区：
文献类型：
--
作者：
Shi-Hui Song;K. Shirasaka;Mami Katayama;Suguru Nagaoka;Shinji Yoshihara;Tomo Osawa;J. Sumaoka;H. Asanuma;M. Komiyama
人工受体的制备，结合肽在水中是最有吸引力的主题之一，因为它们的潜在应用，分离/纯化的生物产品，生物传感，治疗，和其他。然而，合成这些受体的方法往往受到难以将几个识别部分放置在纳米尺度空间的预定位置的阻碍。因此，分子印迹技术经常被采用。2以往的印迹技术主要基于以下三种策略：（1）蛋白质表面结构的印迹;（2）蛋白质暴露区域的短肽序列的印迹;（3）蛋白质识别生物分子作为功能单体。5这些人工受体对模板蛋白表现出选择性亲和力。然而，很少有这些受体区分动态结构的肽在溶液中，虽然许多重要的特性的肽（生物功能，超分子组装，和其他）主要是由这些解决方案的结构。目前还没有一种通用的人工受体设计策略，本文报道了一种新型的受体，它能严格识别寡肽在水中的溶液结构。在模板寡肽的存在下，β-环糊精（β-CyD）的乙烯基单体在水中聚合，并且几个β-CyD分子互补地固定到模板中的非极性和大体积基团（方案1）。在这里使用的寡肽模板中（如图1所示），血管紧张素II（AII）是一种用于人体血压调节的八肽激素。它的前体十肽是血管紧张素I（AI），其通过酶促去除其C-末端His-Leu而转化为活性激素AII。尽管这两种寡肽的氨基酸序列具有明显的相似性，但印迹的β-CyD聚合物清楚地区分了它们在水中的结构差异，并将它们彼此分离。此外，AI和AII中仅一个氨基酸（异亮氨酸）改变为缬氨酸（AIf [Val 5]-AI和AIf [Val 5]-AII）也被印迹聚合物成功识别，因为它们识别这些密切相关的寡肽中的每一个的溶液结构。
Preparation of artificial receptors that bind peptides in water is one of the most attractive themes because of their potential applications to separation/purification of bioproducts, biosensing, therapy, and others. 1 However, synthetic approaches toward these receptors have been often hampered by difficulty in placing several recognition moieties at predetermined positions in nanometer-scaled space. Thus, the molecular imprinting technique was often employed. 2 Most of previous imprintings were based on the following three strategies:(1) imprinting of the surface structure of protein, 3 (2) imprinting of a short oligopeptide sequence in exposed domain of protein, 4 and (3) use of protein-recognizing biomolecule as functional monomer. 5 These artificial receptors showed selective affinity to the template proteins. However, few of these receptors distinguished dynamic structures of peptides in solutions, although many important characteristics of peptides (biological functions, supramolecular assembling, and others) are primarily governed by these solution structures. There has been no general strategy for the design of desired artificial receptors.Here we report new types of receptors which strictly recognize solution structures of oligopeptides in water. In the presence of template oligopeptide, a vinyl monomer of β-cyclodextrin (β-CyD) is polymerized in water, and several β-CyD molecules are immobilized complementarily to apolar and bulky groups in the template (Scheme 1). 6, 7 Of the oligopeptide templates employed here (shown in Figure 1), angiotensin II (AII) is an octapeptide hormone for blood pressure regulation in the human body. Its precursor decapeptide is angiotensin I (AI), which is converted to the active hormone AII by enzymatic removal of its C-terminal His-Leu. In spite of the apparent similarity of amino acid sequences of these two oligopeptides, the imprinted β-CyD polymers clearly distinguish the difference in their structures in water and separate them from each other. Furthermore, alteration of only one amino acid (isoleucine) in AI and AII to valine (AIf [Val5]-AI and AIIf [Val5]-AII) is also successfully recognized by the imprinted polymers, since they recognize the solution structure of each of these closely related oligopeptides.