稀土铈基人工模拟酶调控细胞命运的研究进展

稀土金属尤其是铈的配合物和氧化物纳米粒子因其优异的催化性能而在生物医学领域得到广泛应用。大量的研究证明了基于铈配合物和氧化物纳米粒子的人工模拟酶具有磷酸酶、过氧化氢酶、超氧化物歧化酶、过氧化物酶、氧化酶等酶的活性。近年来,这类人工模拟酶在细胞命运调控领域的应用受到了广泛关注。设计和构建基于铈模拟酶的平台来指导细胞行为可以克服天然酶的固有局限性,提高对细胞命运调控的效果,有效地控制了细胞的黏附、增殖以及分化等行为。     

仿硒酶研究进展

硒是人体中必需的微量元素,它与各种疾病和人类健康息息相关。硒在生物体内以硒代半胱氨酸形式表现其生理活性和功能。为了探索硒在硒蛋白中结构和功能关系并可能发展成硒相关的适用药物,人们付出许多努力来发展硒蛋白模拟化学。由于硒酶—谷胱甘肽过氧化物酶（GPX）重要的抗氧化作用以及潜在的药用价值,国际上广泛开展了对它的人工模拟研究。本文对近年来硒酶模拟化学和生物学相关研究进展进行了综述。     

人工模拟抗体及其在农药残留检测中的应用研究

介绍了人工模拟抗体的概念和制备方法,综述了人工模拟抗体在三嗪类农药、有机磷农药、苯氧羧酸类农药及其他农药残留检测中的应用,并对人工模拟抗体的发展作了展望(引用文献31篇)。     

催化水解反应的肽基模拟酶的活性来源、催化机理及应用

肽基材料由于其与蛋白质高度相似和结构可控等优势,是构建人工模拟酶的一种理想材料;此外,小肽中氨基酸排列的多样性、序列的自组装特性、纳米结构稳定性、结构简单易于设计、良好生物相容性等优势,使得构建具有高效催化活性的肽基模拟酶具有非常好的应用前景。利用肽基材料通过理性设计活性位点来构建模拟酶具有多方面优势:(1) 氨基酸序列可以直接从天然酶中的活性位点获得,保留酶的功能,但降低了酶固有的复杂性;(2) 肽序列中可以嵌入各种具有特定结构及功能的活性位点,便于对模拟酶进行人工理性设计;(3) 肽具有良好的生物相容性,可以在温和条件下催化反应进行。根据催化降解化学键的不同,可将肽基水解模拟酶分为以下几种:催化酯键降解的肽基模拟酶、催化肽键降解肽基模拟酶、催化糖苷键水解的肽基模拟酶。本文主要分析了具有水解酶活性的肽基模拟酶的活性来源、构建方法及微观结构、催化反应类型、催化影响因素、活性改善方法、作用机理及未来潜在应用等;以期为构建具有高效水解催化活性的模拟酶提供借鉴,推进肽基水解模拟酶的研究发展及实际应用。     

奇异的分子胶囊——环糊精研究概况

仿生化学,近年来成为化学领域的前沿阵地之一。模拟酶与生物膜的功能研究,有美好的前景。生物体内的呼吸、代谢、合成蛋白质、转运等种类繁多的全部物质转换和能量转换过程,依赖于各种酶。在古典有机合成中难以实现的反应,依靠酶的惊人的催化能力,可以在水溶液中、常温下,高效率、特异地进行。特别是在能源日益紧张的今日,许多化学家在向生物体“学习”有机合成,孜孜不倦地进行人工模拟     

SOD模拟及其抗氧化和抗炎症功能的研究进展*

超氧化物歧化酶(superoxide dismutase, 简称SOD) 作为生物体内超氧离子自由基的清除剂, 具备有效抗氧化、抗炎症、抗衰老之功效, 并用于临床, 其化学模拟引起了人们的广泛研究兴趣。本文将简要介绍近年来SOD 人工模拟酶及其生物医学活性研究所取得的重要进展, 特别是Cu,Zn-SOD 模拟物结构与功能的相互关系、Mn-SOD 模拟物的生物活性及其医学应用。     

自然和人工光合作用水裂解催化剂

近年生物光合作用水裂解催化中心的结构研究取得重要进展,为人工模拟光合作用水裂解研究提供了理想的蓝图。人工模拟生物水裂解催化中心、制备高效和廉价的人工水裂解催化剂、获得电能和(或)氢能被认为是解决人类所面临的能源危机和环境污染问题的理想途径。这方面的研究具有重要科学意义和应用价值,同时也是广受关注的重大科学前沿。本文对最近生物水裂解催化中心和其人工模拟研究进展进行了评述。     

分子印迹模拟酶的制备与应用研究

分子印迹模拟酶是应用分子印迹技术合成的对目标分子具有特异性催化活性的聚合物,具有良好的化学和物理稳定性、结构预定性以及实用性。本文主要介绍了分子印迹模拟酶的构建策略,包括印迹过渡态类似物、印迹底物或底物类似物和其他构建途径;探讨了分子印迹模拟酶的制备方法,总结了分子印迹模拟酶在催化反应方面的应用,涉及有机合成催化、食品安全危害物分解、环境污染物降解和临床医学检验等。     

酶催化原子转移自由基聚合

原子转移自由基聚合(ATRP)是制备分子量以及分散度可控聚合物的重要途径。然而,受制于除氧步骤复杂、金属催化剂残留以及单体适用范围有限等因素,ATRP难以应用于批量制备功能化聚合物/共聚物材料,限制了其进一步应用。近年来提出和发展的酶催化聚合,为高效便捷除氧、拓展单体适用范围以及制备具有特殊(纳米)结构的纯净聚合物/共聚物提供了新思路。本文详细介绍了酶的结构与催化机理,以酶的种类进行分类,系统总结了具有不同结构的酶催化体系(包括过氧化辣根酶、血红蛋白、血红素、漆酶等)的催化机理、适用单体、优缺点及应用等;综述了酶以及酶模拟物催化ATRP体系的发展现状;最后,对酶催化ATRP的发展前景和挑战进行了探讨和展望。     

具有甲状腺素脱碘酶活性的抗体酶的化学修饰

甲状腺素脱碘酶是一种膜硒蛋白[1], 它能够将甲状腺素降解为不同产物, 并对甲状腺素的生理功能起调控作用. 但是, 甲状腺素脱碘酶极易变性失活, 到目前为止仍未得到纯酶[2]. 近来, 此酶的人工模拟工作逐渐成为热点. 我们小组[3]首次以3,5,3′,5′-四碘甲状腺原氨酸五水钠盐(T4)为半抗原, 采用单克隆抗体技术和苯甲基磺酰氟及硒氢化钠修饰的方法, 成功地制备了具有甲状腺素脱碘酶活性的抗体酶.     

Modification of Cyclodextrins for Use as Artificial Enzymes

The magical powers of enzymes have been attributed to their ability to bind specific substrates and catalyze reactions of the bound substrate. Artificial enzymes synthetically mimic the binding and the catalytic site to produce molecules that are not only smaller in size but also potentially have similar activity to the real enzymes. The main objective of our research is to create artificial redox enzymes by using cyclodextrins as binding sites and attaching flavin derivatives as the catalytic site. We have developed a strategy to attach a catalytic site to cyclodextrin exclusively at the 2-, 3- or the 6-position. The evaluation of the artificial enzyme in which flavin is attached to the 2-position gives a 647-fold acceleration factor. Although this is modest compared to those of real enzymes (which can have acceleration factors of a trillion), the artificial enzymes allow us to understand the elements that contribute to the incredible catalytic power of enzymes.     

Integration of ion channel proteins into a polymer matrix – investigation by the patch‐clamp technique

Two types of natural ion channel proteins, gramicidin A and nicotinic acetylcholine receptor, were reconstituted into an artificial lipid/polymer matrix. The functionality of the proteins was fully maintained after the integration. Particular kinds of phospholipids and of polymer matrices had been chosen to set up the artificial mimic system, which itself constitutes a novel type biosensor. The functionality of the mimic system was verified by single channel patch‐clamp measurements.     

Self‐Assembly and Compartmentalization of Nanozymes in Mesoporous Silica‐Based Nanoreactors

Herein, to mimic complex natural system, polyelectrolyte multilayer (PEM)‐coated mesoporous silica nanoreactors were used to compartmentalize two different artificial enzymes. PEMs coated on the surface of mesoporous silica could serve as a permeable membrane to control the flow of molecules. When assembling hemin on the surface of mesoporous silica, the hemin‐based mesoporous silica system possessed remarkable peroxidase‐like activity, especially at physiological pH, and could be recycled more easily than traditional graphene–hemin nanocompounds. The hope is that these new findings may pave the way for exploring novel nanoreactors to achieve compartmentalization of nanozymes and applying artificial cascade catalytic systems to mimic cell organelles or important biochemical transformations     

Preorganization boosts the artificial esterase activity of a self-assembling peptide

The creation of artificial enzymes to mimic natural enzymes remains a great challenge owing to the complexity of the structural arrangement of the essential amino acids in catalytic centers. In this study, we used the phosphatase-based enzyme-instructed self-assembly(EISA) to supervise artificial esterases' final structures and catalytic activities. We reported that peptide precursors containing different phosphorylation sites could preorganize into alternated nanostructures and undergo dephosphorylation in the presence of alkaline phosphatase(ALP) with variation in kinetic and thermodynamic profiles. Although identical self-assembly compositions were formed after dephosphorylation, precursors with more enhanced preorganized states tended to better promote ALP dephosphorylation, facilitate further self-assembly, and strengthen the catalytic activities of the final assemblies. We envisioned that our strategy would be useful for further construction and manipulation of various artificial enzymes with superior catalytic activities.     

人工硒酶设计新策略

作为人体内重要的抗氧化酶,谷胱甘肽过氧化物酶受到人们越来越多的关注.为探索其催化机制,并开发极具潜力的抗氧化药物,国际上广泛开展了人工模拟谷胱甘肽过氧化物酶的研究工作.基于化学、生物学、超分子科学以及纳米科学及其深度交叉,人们研究构建了从小分子到大分子,再到纳米等不同结构的谷胱甘肽过氧化物酶模拟物.本文主要综述本研究组和其他研究组基于以大分子为骨架设计人工谷胱甘肽过氧化物酶的研究思路和策略.研究体系包括合成的大分子硒酶模型、自组装大分子硒酶模型和生物大分子硒酶模型等.     

Boolean Logic Networks Mimicked with Chimeric Enzymes Activated/Inhibited by Several Input Signals

Reactions catalyzed by artificial allosteric enzymes, chimeric proteins with fused biorecognition and catalytic units, were used to mimic multi-input Boolean logic systems. The catalytic parts of the systems were represented by pyrroloquinoline quinone-dependent glucose dehydrogenase (PQQ-GDH). Two biorecognition units, calmodulin or artificial peptide-clamp, were integrated into PQQ-GDH and locked it in the OFF or ON state respectively. The ligand-peptide binding cooperatively with Ca²⁺ cations to a calmodulin bioreceptor resulted in the enzyme activation, while another ligand-peptide bound to a clamp-receptor inhibited the enzyme. The enzyme activation and inhibition originated from peptide-induced allosteric transitions in the receptor units that propagated to the catalytic domain. While most of enzymes used to mimic Boolean logic gates operate with two inputs (substrate and co-substrate), the used chimeric enzymes were controlled by four inputs (glucose – substrate, dichlorophenolindophenol – electron acceptor/co-substrate, Ca²⁺ cations and a peptide – activating/inhibiting signals). The biocatalytic reactions controlled by four input signals were considered as logic networks composed of several concatenated logic gates. The developed approach allows potentially programming complex logic networks operating with various biomolecular inputs representing potential utility for different biomedical applications.     

Construction of Supramolecular Nanostructures with High Catalytic Activity by Photoinduced Hierarchical Co-Assembly

Inspired by natural enzymes, hierarchical catalytic supramolecular nanostructures were developed by the co-assembly of hemin and glucose oxidase (or Au NPs) with the photosensitive ferrocene–tyrosine (Fc-Y) molecule. Illuminated by white light, the Fc-Y molecules are polymerized and co-assemble with hemin into truncated polyhedrons. The Au NPs grew in situ at the surface of the co-assembled polyhedrons, achieving ordered supramolecular nanostructures. Because the Au NPs can serve as an artificial glucose oxidase and the hemin could act as a peroxidase mimic, the supramolecular hybrid nanostructures were used to mimic natural enzymes and catalyze the glucose conversion cascade reaction. The hybrid Au NPs@Fc-Y&hemin polyhedrons showed superior catalytic activity, good reusability, and maintained the catalytic activity over a wide temperature and pH range. The study demonstrates a feasible strategy to construct hierarchical co-assembled supramolecular nanostructures as multi-enzyme mimics, with potential applications in biocatalysis and biosensing.     

联二萘酚类磷酸吡哆醛模拟酶的合成与应用研究进展

模拟酶化合物的合成与应用研究具有重要的理论和实际意义。近年来研究的一些联二萘酚类磷酸吡哆醛模拟酶具有氨基酸构型转换的功能,并可用于手性氨基醇的对映选择性识别。本文简要介绍了该类化合物的合成方法,综述了近年来联二萘酚类磷酸吡哆醛模拟酶在手性氨基酸构型转换、手性氨基醇对映选择性识别以及萃取拆分等方面的应用。     

Biosynthetic approach to modeling and understanding metalloproteins using unnatural amino acids

Metalloproteins have inspired chemists for many years to synthesize artificial catalysts that mimic native enzymes.As a complementary approach to studying native enzymes or making synthetic models,biosynthetic approach using small and stable proteins to model native enzymes has offered advantages of incorporating non-covalent secondary sphere interactions under physiological conditions.However,most biosynthetic models are restricted to natural amino acids.To overcome this limitation,incorporating unnatural amino acids into the biosynthetic models has shown promises.In this review,we summarize first synthetic,semisynthetic and biological methods of incorporates unnatural amino acids(UAAs)into proteins,followed by progress made in incorporating UAAs into both native metalloproteins and their biosynthetic models to fine-tune functional properties beyond native enzymes or their variants containing natural amino acids,such as reduction potentials of azurin,O_2 reduction rates and percentages of product formation of HCO models in Mb,the rate of radical transport in ribonucleotide reductase(RNR)and the proton and electron transfer pathways in photosystemⅡ(PSⅡ).We also discuss how this endeavour has allowed systematic investigations of precise roles of conserved residues in metalloproteins,such as Metl21 in azurin,Tyr244 that is cross-linked to one of the three His ligands to CuB in HCO,Tyr122,356,730 and 731 in RNR and TyrZ in PSⅡ.These examples have demonstrated that incorporating UAAs has provided a new dimension in our efforts to mimic native enzymes and in providing deeper insights into structural features responsible high enzymatic activity and reaction mechanisms,making it possible to design highly efficient artificial catalysts with similar or even higher activity than native enzymes.     

Comments on recent achievements in biomimetic organic synthesis

The appealing beauty of the routes that Nature uses to build natural products is breath taking and the quest for laboratory syntheses that mimic these routes is longstanding. Since Robert Robinson introduced the concept of biomimetic synthesis in 1917, debates have been conducted about the participation of specific enzymes in every step of the biogenesis of every class of natural product. The successful synthesis of many natural products often follows routes analogous to processes that occur in the living cell with minimum enzyme participation. It should not be concluded, however, that we are only able to imitate biogenetic processes in which enzymes are not involved. Perhaps the most appealing facet of a biomimetic strategy is that it pursues the development of synthetic methodology inspired by biogenesis, even if the mimicked biogenetic route is only hypothetical. Improved biogenetic syntheses could be brought about by artificial enzymes that catalyze specific transformations.