基于核酸适体的外泌体分子识别研究进展

自研究者证实外泌体承担了细胞外RNA等物质的运输功能以来, 关于外泌体来源与功能的研究一直备受关注. 近年来外泌体被发现具有作为疾病生物标志物的潜力, 使得拥有特定表面蛋白以及特定装载物的外泌体成为分析化学领域有价值的检测对象. 从化学本质角度来说, 外泌体的获取与分析需要依赖特异性的分子识别过程. 核酸适体作为分子识别单元, 因其特异性强、 亲和力高、 生物活性稳定、 易于合成和保存、 而且其序列和结构上具有可编程性, 易于设计和修饰, 已成功地用在外泌体相关的生物传感体系中. 本文从外泌体的化学组成及其具有生理、 病理意义的组分出发, 从外泌体通用生物标志物识别、癌细胞来源外泌体的检测及外泌体蛋白谱的分析这3个方面综述了以核酸适体作为分子识别单元在外泌体分析领域的代表性工作, 总结了现有的靶向外泌体的核酸适体序列信息以及应用场景, 阐述了利用化学合成与修饰以及DNA自组装等化学调控手段增强核酸适体分子识别性能的最新进展, 并从适用于外泌体分子识别的核酸适体的筛选以及化学修饰的角度, 对未来的研究方向进行了展望.     

核酸适体靶向的膜蛋白识别与功能调控研究进展

膜蛋白在细胞生命活动中发挥着重要作用, 研究并调控细胞膜蛋白的结构和功能有助于阐明生命活动的基本规律, 为新型药物研发和高效疾病诊治提供研究基础. 核酸适体是一类特殊的寡核苷酸序列, 因具有特异性识别靶标的能力而被广泛用于生物传感领域. 将核酸适体与DNA纳米技术相结合, 利用DNA分子可程序化设计、 可功能化修饰等优势, 发展核酸适体靶向的膜蛋白识别与功能调控方法可为研究膜蛋白相互作用提供有力工具. 本文介绍了基于核酸适体靶向识别的DNA纳米技术在膜蛋白识别及细胞功能调控中的研究进展, 并对核酸适体靶向的膜蛋白识别及功能调控领域面临的挑战进行了分析, 对其应用前景进行了展望.     

基于分子识别的细菌检测研究进展

以抗体-抗原免疫识别、 核酸碱基互补配对识别以及核酸适体-配体识别这3种分子识别方式分类, 综述了近几年基于分子识别的细菌检测研究工作进展, 总结了细菌检测相关研究存在的一些挑战, 并展望了该领域的发展前景.     

Recent Progress on Highly Selective and Sensitive Electrochemical Aptamer-based Sensors

Highly selective, sensitive, and stable biosensors are essential for the molecular level understanding of many physiological activities and diseases. Electrochemical aptamer-based (E-AB) sensor is an appealing platform for measurement in biological system, attributing to the combined advantages of high selectivity of the aptamer and high sensitivity of electrochemical analysis. This review summarizes the latest development of E-AB sensors, focuses on the modification strategies used in the fabrication of sensors and the sensing strategies for analytes of different sizes in biological system, and then looks forward to the challenges and prospects of the future development of electrochemical aptamer-based sensors.     

Aptamer-based label-free method for hemin recognition and DNA assay by capillary electrophoresis with chemiluminescence detection

An aptamer-based label-free approach to hemin recognition and DNA assay using capillary electrophoresis with chemiluminescence detection is introduced here. Two guanine-rich DNA aptamers were used as the recognition element and target DNA, respectively. In the presence of potassium ions, the two aptamers folded into the G-quartet structures, binding hemin with high specificity and affinity. Based on the G-quartet–hemin interactions, the ligand molecule was specifically recognized with a K _d ≈ 73 nM, and the target DNA could be detected at 0.1 μM. In phosphate buffer of pH 11.0, hemin catalyzed the H₂O₂-mediated oxidation of luminol to generate strong chemiluminescence signal; thus the target molecule itself served as an indicator for the molecule–aptamer interaction, which made the labeling and/or modification of aptamers or target molecules unnecessary. This label-free method for molecular recognition and DNA detection is therefore simple, easy, and effective. Figure A label-free approach to aptamer-based hemin recognition and DNA detection is introduced, which gives great potential for using a small molecule itself as the indicator for molecular recognition and DNA detection thereby avoiding any labeling or modification step     

分子印迹聚合物研究:从小分子到生物大分子

分子印迹技术是一项制备功能聚合物材料的方法,其对印迹分子的专一性选择识别能力引起了人们的广泛关注。随着方法的基本确立和技术的逐渐成熟,其应用领域和范围不断扩大。本文在总结以往研究结果的基础上,对迄今为止进展相对缓慢的生物大分子印迹研究予以了特别关注,对相关的水环境下的分子识别问题进行了仔细的讨论,认真的分析了生物大分子印迹研究工作的难点和不利因素,对分子印迹技术的未来发展和应用前景进行了展望。     

Synthesis of Glycopeptides,Partial Structures of Biological Recognition Components [New Synthetic Methods (67)]

Glycopeptides are partial structures of the connecting regions of glycoproteins and, like these, always contain glycosidic bonds between the carbohydrate and peptide parts. Glycoproteins are not only widely distributed but are also decisive factors in post-translational biological selectivity, especially in biological recognition. Targeted syntheses of glycopeptides require stereoselective formation of the glycosidic bonds between the carbohydrate and the peptide parts and protective group methods that enable selective deblocking of only one functional group in these polyfunctional molecules. These heavy demands have been met by the well-established use of benzylic protective groups, which can be removed by hydrogenolysis, combined with the use of base-labile 2-phosphonioethoxycarbonyl (Peoc) or 9-fluorenylmethoxycarbonyl (Fmoc) protective groups or of bromoethyl esters, which can be removed under neutral conditions. The acidolysis of tert-butyloxycarbonyl (Boc) groups and of tert-butyl esters has also been successfully used, although, under acidic conditions, anomerization or rupture of the glycosidic bonds may occur, especially when nucleophiles are present. The stable, two-stage 2-(pyridyl)ethoxycarbonyl (Pyoc) protective groups allow a more reliable synthesis of complex glycopeptides since they can be removed, after modifications, under mild conditions. Particularly suitable for the synthesis of sensitive glycopeptides are the stable allyl protective groups. They can be removed from the complex glycopeptides in a highly selective and effective manner by means of noble-metal catalysts under practically neutral conditions. These methods have been employed to synthesize glycopeptides corresponding to partial structures of interesting glycoproteins. Deprotected glyopeptides representing tumor-associated antigen structures can be coupled to bovine serum albumin, which serves as a biological carrier molecule, without the necessity of using an artificial coupling component (spacer).     

环糊精用于分子识别分析的新进展

本文概述了环糊精用于分子识别分析的新进展，讨论了单体、修饰、交联环糊精在分子识别分析中的具体应用与展望。     

Progress in DNA Aptamers as Recognition Components for Protein Functional Regulation

Proteins play a central role in all domains of life, and precise regulation of their activity is essential for understanding the related biological processes and therapeutic functions. Nucleic acid aptamers, the molecular recognition components derived from systematic evolution of ligands by exponential enrichment(SELEX), can specifically identify proteins with antibody-like recognition characteristics and help to regulate their activity. This minireview covers the SELEX-based selection of protein-binding aptamers, membrane protein analytical techniques based on aptamer-mediated target recognition, aptamer-mediated functional regulation of proteins, including membrane receptors and non-membrane proteins(thrombin as a model), as well as the potential challenges and prospects regarding aptamer-mediated protein manipulation, aiming to supply some useful information for researchers in this field.     

Glycopolymers and Glyco‐nanoparticles in Biomolecular Recognition Processes and Vaccine Development

With advances in polymerization techniques as well as selective chemical modification of carbohydrates, glycopolymers and glyco‐nanoparticles are emerging as an important class of materials with tailored properties or novel nanotechnology‐based platforms for a number of applications. The field of the so‐called glyco‐nanotechnology is starting to show some promises for future clinical applications. Glyco‐nanoparticles, due to their versatile nature, could offer a platform for the design of carbohydrate‐based vaccines and possibly allow the development of new single‐dose vaccines in disease areas of unmet need. This paper surveys the emerging roles of carbohydrate‐based polymeric and nanomaterials for biomolecular recognition processes and vaccine development.

     

卟啉及其衍生物对生物分子的识别研究进展

卟啉及其衍生物作为主体分子对生物分子的识别具有独特的优点：分子结构多样、形状选择、稳定性好和敏感性高等。 本文着重介绍了国内外关于卟啉对DNA、氨基酸、醌和胺等的分子识别研究进展。     

Molecular Architecture and Function of Polymeric Oriented Systems: Models for the Study of Organization,Surface Recognition,and Dynamics of Biomembranes

The Part and the Whole. The principle of self-organization for the creation of functional units is not an invention of modern natural sciences. It was already a basic idea of the ancient philosophies in Asia and Europe: only the mutuality of the parts creates the whole and its ability to function. Translated into the language of chemistry this means: the self-organization of molecules leads to supramolecular systems and is responsible for their functions. Thermotropic and lyotropic liquid crystals are such functional units, formed by self-organization. As highly oriented systems, they exhibit new properties. The importance of lyotropic liquid crystals for the life sciences has been known for a long time. They are a prerequisite for the development of life and the ability of cells to function. In materials sciences this concept of function through organization led to the development of new liquid-crystalline materials. From the point of view of macromolecular chemistry, this review tries to combine these two different fields and especially hopes to stimulate their interaction and joint treatment. To exemplify this, the molecular architecture of polymeric organized systems will be discussed. Polymeric liquid crystals combine the ability to undergo spontaneous self-organization–typical of liquid-crystalline phases–with the polymer-specific property of stabilizing these ordered states. As new materials, polymeric liquid crystals have already been investigated intensively. As model systems for biomembranes as well as for the simulation of biomembrane processes, they so far have been little discussed. The intention of this review article is to show that polymer science is able to contribute to the simulation of cellular processes such as the stabilization of biomembranes, specific surface recognition, or even the “uncorking” of cells. Polymer science, having an old tradition as an inter-disciplinary field, can no longer restrict itself to common plastics. Attempts to reach new horizons have already begun. The borderland between liquid crystals and cells will certainly play an important role. Basic requirements to work in this frontier area between organic chemistry, membrane biology, life science, and materials science will be the delight in scientific adventures as well as the courage to go ahead. The most important prerequisite will be the willingness to cooperate with disciplines which so far have not really accepted each other. From this point of view, this review does not aim at giving defined answers. It wants instead to encourage the scientific venture: too often we cling to painfully acquired knowledge, fearing adventures.     

A Hairpin Electrochemical Aptasensor for Sensitive and Specific Detection of Thrombin Based on Homogenous Target Recognition

An electrochemical aptasensor was developed for sensitive and specific detection of thrombin by combining homogenous recognition strategy and gold nanoparticles (AuNPs) amplification. Streptavidin‐alkaline phosphatase was used as reporter molecule. Compared with the traditional hairpin aptasensor monitoring the distance of the redox molecule from the electrode surface, the proposed aptasensor successfully overcome the limitations of distance and improved the stability and high affinity of the aptamer hairpin through homogenous recognition, which enhanced the sensitivity and selectivity of the sensors effectively. Additionally, AuNPs were employed to increase the active area and conductivity of the electrode, thus, improving the sensitivity of the aptasensor. As a result, the designed thrombin detection sensor obtained a lower detection limit of 0.52 pM in buffer and 6.9 pM in blood serum.     

化学及生物体系中的分别识别*

分子识别的目标是研究分子间专一性地相互作用, 这在化学及生命过程中起着非常重要的作用。本文综述了分子识别的机制及其在化学、生命科学、材料、信息等有关学科中的应用。     

尼卡地平分子聚合物的制备及识别性能研究

采用分子印迹技术合成了以尼卡地平为模板分子,甲基丙烯酸为功能单体的分子印迹聚合物(MIP).运用平衡结合实验研究了聚合物的吸附特性和选择识别能力.通过Scatchard方程分析,结合位点的离解常数Kd=1.03 mmol·L-1,最大表观结合常数Qmax=18.76 μmol·g-1.结果表明,分子印迹聚合物对尼卡地平呈现出较高的吸附性和选择识别性,对尼卡地平药物的分离富集和检测具有实际临床意义.     

Studies on the Process of Molcular Recognition directed Self-Assembling between Melamine and Light Active Barbituric Acid Derivatives

The process of molecular recognition directed self-assembling between two complementary molecular components. 5-(4-dodecyloxybenzylidene)-2,4,6-(1H, 3H)-pyrimidinetrione (B) and 4-amino-2,6-didodecylamino-l,3,5-triazine (M),was studied using fluorescence spectroscopy. It was found that it took more than 1200 h for this process to reach the equilibrium.This means that there must be other kinds of noncovalent interactions besides hydrogen bonds.This system has a positive cooperativity and B is proved to be as both the fluorescence probe and molecular components of the self-assembling.     

晶状体蛋白识别互作与白内障的研究进展

白内障是全球致盲率最高的眼科疾病, 发病组织为晶状体. 晶状体内纤维细胞含有高浓度的晶状体蛋白, 晶状体蛋白家族分α?, β?和γ?3大亚家族. α-晶状体蛋白具有小分子伴侣功能, 可识别错误折叠蛋白质, 维持晶状体内蛋白质稳态; β?/γ?晶状体蛋白通过分子内或分子间相互作用, 主要发挥结构蛋白功能. 晶状体蛋白在晶状体纤维细胞内呈瞬时有序排列, 精准分子识别及动态相互作用在维持晶状体透明度中发挥关键作用. 晶状体内蛋白质稳态失衡是白内障的主要致病因素. 晶状体蛋白半衰期长, 且翻译合成后不再更新, 广泛受pH值、 金属离子、 辐射损伤和蛋白质翻译后修饰等细胞内外环境因素和化学因素的干扰, 影响晶状体蛋白间的分子识别和相互作用, 诱发白内障. 理清化学调控的晶状体蛋白分子识别及互作调控, 有助于阐明白内障发病机理, 并发掘防治白内障的创新策略. 本文基于晶状体蛋白识别互作与白内障研究进展, 综合评述了晶状体蛋白的分子识别、 相互作用方式、 调控因素及研究技术创新, 并探讨了晶状体蛋白识别互作调控网络在白内障药物研发的应用价值与挑战.     

基于核酸适体与互补核酸和目标蛋白之间竞争反应的PDGF蛋白特异性识别

报道了一种利用核酸适体与互补核酸和目标蛋白之间的竞争反应用于PDGF蛋白的特异性识别方法.采用反相微乳液技术制备了包覆有亚甲基蓝(MB)的SiO2纳米复合物(SiO2-MB),利用固定在磁性纳米颗粒上的核酸适体与SiO2-MB纳米颗粒标记的互补核酸进行杂交反应,将一定数量的SiO2-MB纳米颗粒固定于磁性纳米颗粒的表面...     

表面增强喇曼光谱技术应用于生物体系的最新进展

本文综述了近几年来表面增强喇曼光谱技术应用于以下几个方面的生物体系的最新资料：（１）核酸及其组分，（２）蛋白质及其组分，（３）儿茶酚胺，（４）有色生物质，（５）膜制品。总结了表面增强喇曼光谱技术的一般性结论，并对这一技术应用于生物体系的发展作了展望     

利凡诺分子模板聚合物的吸附与识别特性研究

以利凡诺药物为模板分子,α-甲基丙烯酸为功能基单体,乙二醇二甲基丙烯酸酯为交联剂,选用分子模板技术,合成了一种新的具有类似于酶或药物受体结合部位为结构特征的分子模板聚合物.研究了它对利凡诺和其它底物的吸附特性和选择性识别能力.结果表明,与组成相同的非模板聚合物相比,利凡诺分子模板聚合物有较大的吸附性能和高度的选择性及识别能力.静电作用和氢键在吸附和识别过程中发挥着重要作用.