分子钳人工受体研究进展

分子识别是生物体系的基本特征, 并在生命活动中起中心作用. 利用合成的人工受体与适当底物间的分子识别以建立化学模型或化学仿生体系对生命过程中的分子识别现象进行模拟研究是生物有机化学和超分子化学前沿富于挑战的课题之一. 按照不同的隔离基, 综述了分子钳人工受体的研究进展.     

新型希夫碱型钳形人工受体的微波合成及其对中性分子的识别性能

以对苯二甲酸为起始原料,设计并合成了8个新型的芳环钳形人工受体(3a～3h),其结构经1H NMR,IR,ESI-MS和元素分析表征。利用UV-Vis滴定法初步考察了3a～3h对中性分子(邻苯二胺,间苯二胺,对苯二胺和二苯甲酮)的识别性能,结果表明3a～3h对其具有良好的识别性能。     

Molecular Recognition of Zwitterions with Artificial Receptors

Many biomolecules exist as internal ion pairs or zwitterions within a biologically relevant pH range. Despite their importance, the molecular recognition of this type of systems is specially challenging due to their strong solvation in aqueous media, and their trend to form folded or self‐assembled structures by pairing of charges of different sign. In this Minireview, we will discuss the molecular recognition of zwitterions using non‐natural, synthetic receptors. This contribution does not intend to make a full in‐depth revision of the existing research in the field, but a personal overview with selected representative examples from the recent literature.     

甘脲类分子胶囊受体合成方法的研究进展

甘脲类分子胶囊是一类独特的由非共价键弱相互作用力组装而成的人工受体, 在分子识别、自组装、分子微反应器、智能材料等方面得到了广泛而深入的研究. 系统综述了网球型(Tennis ball)、垒球型(Softball)、足球型(Football)及圆盘型(Jelly Doughnut)等分子胶囊的合成方法.     

Artificial Signal Transduction with Primary and Secondary Messengers

The complete, entirely artificial, signal‐transduction process was realized with a pair of tailored transmembrane units that were equipped with receptor‐ and reactive sites at both amphiphilic ends. Thus, docking of the primary messenger, transmission of the signal, and release of the secondary messenger could all be imitated in a single experimental setup. The system imitates the signaling principle of receptor tyrosine kinases and employs bisphosphonate head‐groups for oligoamine‐recognition and a pair of thiol nucleophiles and pyridine disulfide tail‐groups for intravesicle S_N2 displacement. This system operates in a unidirectional fashion, does not suffer from intervesicle competition, and is highly sensitive towards the lipid composition of the membrane and the nature of the primary messenger.     

Computational Methods for Understanding the Selectivity and Signal Transduction Mechanism of Aminomethyl Tetrahydronaphthalene to Opioid Receptors

Opioid receptors are members of the group of G protein-couple receptors, which have been proven to be effective targets for treating severe pain. The interactions between the opioid receptors and corresponding ligands and the receptor’s activation by different agonists have been among the most important fields in opioid research. In this study, with compound M1, an active metabolite of tramadol, as the clue compound, several aminomethyl tetrahydronaphthalenes were designed, synthesized and assayed upon opioid receptors. With the resultant compounds FW-AII-OH-1 (Ki = 141.2 nM for the κ opioid receptor), FW-AII-OH-2 (Ki = 4.64 nM for the δ opioid receptor), FW-DI-OH-2 (Ki = 8.65 nM for the δ opioid receptor) and FW-DIII-OH-2 (Ki = 228.45 nM for the δ opioid receptor) as probe molecules, the structural determinants responsible for the subtype selectivity and activation mechanisms were further investigated by molecular modeling and molecular dynamics simulations. It was shown that Y^7.43 was a key residue in determining the selectivity of the three opioid receptors, and W^6.58 was essential for the selectivity of the δ opioid receptor. A detailed stepwise discovered agonist-induced signal transduction mechanism of three opioid receptors by aminomethyl tetrahydronaphthalene compounds was proposed: the 3–7 lock between TM3 and TM7, the DRG lock between TM3 and TM6 and rearrangement of I^3.40, P^5.50 and F^6.44, which resulted in the cooperative movement in 7 TMs. Then, the structural relaxation left room for the binding of the G protein at the intracellular site, and finally the opioid receptors were activated.     

胆甾类人工受体的分子识别研究进展

人工受体分子识别研究是生物有机化学的前沿领域之一。综述了近年来以胆甾 为构筑单元建造的人工受体在分子识别方面的研究进展。     

Cholesteric Molecular Tweezer Artificial Receptor for Rapid and Highly Selective Detection of Ag+ in Food Samples

Chiral cholesteric molecular tweezer 7a was synthesized, and its recognition properties for Ag⁺, Al³⁺, Ca²⁺ etc., were investigated by UV and fluorescence spectra. The results showed that in ethanol/Tris (1/1, v/v, pH 7.0) buffer solution, the host molecular tweezer 7a had a specific recognition ability for Ag⁺, the detection limit was up to 1 × 10⁻⁶ mol/L, and other metal ions had little effect on Ag⁺ recognition. At the same time, the naked-eye detection of Ag⁺ was realized by the light red color of the complex solution. Furthermore, the mechanism of recognition of Ag⁺ by molecular tweezer 7a was studied by a nuclear magnetic titration test and computer molecular simulation, and a rapid detection method of Ag⁺ using host molecular tweezer 7a was established. Through the determination of Ag⁺ in milk powder, quinoa and other food samples, it was proved that this novel method had a good application prospect for the detection of Ag⁺ in food.     

Molecular Recognition and Catalysis: from Macrocyclic Receptors to Molecularly Imprinted Metal Complexes

Summary: The results of studying a number of reactions catalyzed by several types of soluble macromolecular catalytic systems capable of selectively binding organic substrates, namely, modified cyclodextrins, calixarenes and dendrimers are presented. The use of modified cyclodextrins as components of a catalytic system in the phenol and benzene hydroxylation by hydrogen peroxide allows one both to increase the catalytic activity and to change significantly the chemical selectivity. Phosphorilated calixarene – Rh catalytic systems was found to be catalytically active in hydroformylation of linear alkenes C₇–C₁₂. The results of experiments on the oxidation of C₇–C₁₆ alkenes show that, when the ligand is the dendrimer molecule, the fraction of forming methyl ketones substantially increases for the substrates C₇–C₉. For the higher alkenes, this effect is not observed.     

囊泡表面分子间通讯交流体系的构建: 利用受体的分子识别行为调控酶的活性

在人工双层膜囊泡表面, 构建了一个通过人工受体的分子识别行为控制酶反应活性的超分子体系. 体系以生物体细胞信号转导系统为模拟原型, 由作为受体的烷基胺、被受体识别的信号分子吡哆醛衍生物、乳酸脱氢酶、受体和酶之间的媒介物Cu^2＋以及作为体系载体的合成肽脂囊泡五个成分构成．通过UV-vis光谱法及动态光散射测定对体系进行了评价, 结果表明: 随着受体疏水参数增大, 其对信号分子的识别能力增强, 二者呈良好的线性关系; 通过信号分子与囊泡表面静电相互作用的研究表明信号分子具有选择性; 媒介物与信号分子–受体可形成化学计量比为1∶2的配合物, 其形成能力比媒介物与酶的结合能力更强．作为结论, 体系中烷基胺受体对磷酸吡哆醛信号分子的识别有效控制了处于囊泡表面的乳酸脱氢酶的活性．     

Cycloalkyl Groups as Building Blocks of Artificial Carbohydrate Receptors: Studies with Macrocycles Bearing Flexible Side-Arms

The cyclopentyl group was expected to act as a building block for artificial carbohydrate receptors and to participate in van der Waals contacts with the carbohydrate substrate in a similar way as observed for the pyrrolidine ring of proline in the crystal structures of protein-carbohydrate complexes. Systematic binding studies with a series of 1,3,5-trisubstituted 2,4,6-triethylbenzenes bearing various cycloalkyl groups as recognition units provided indications of the involvement of these groups in the complexation process and showed the influence of the ring size on the receptor efficiency. Representatives of compounds that exhibit a macrocyclic backbone and flexible side arms were now chosen as further model systems to investigate whether the previously observed effects represent a general trend. Binding studies with these macrocycles towards β-D-glucopyranoside, an all-equatorial substituted carbohydrate substrate, included ¹H NMR spectroscopic titrations and microcalorimetric investigations. The performed studies confirmed the previously observed tendency and showed that the compound bearing cyclohexyl groups displays the best binding properties.     

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。     

酰氨基硫脲类新型分子钳受体的合成及其对氟离子的识别性能研究

本文设计并高产率合成了三种新型阴离子识别受体化合物,它们对F-的识别选择性较卤素其他阴离子的高。其对F-的识别性能通过紫外—可见光谱和核磁共振氢谱进行了检测,光谱数据表明,在DMSO溶液中受体与F-通过氢键相互作用形成1:1配合物。与以前我们报道的受体化合物相比,由于此类分子钳受体化合物具有更多的阴离子识别位点,因此具有更好地阴离子识别性能。     

Molecular Recognition of Nucleotides in Water by Scorpiand‐Type Receptors Based on Nucleobase Discrimination

The detection of nucleotides is of crucial importance because they are the basic building blocks of nucleic acids. Scorpiand‐based polyamine receptors functionalized with pyridine or anthracene units are able to form stable complexes with nucleotides in water, based on coulombic, π–π stacking, and hydrogen‐bonding interactions. This behavior has been rationalized by means of an exploration with NMR spectroscopy and DFT calculations. Binding constants were determined by potentiometry. Fluorescence spectroscopy studies have revealed the potential of these receptors as sensors to effectively and selectively distinguish guanosine‐5′‐triphosphate (GTP) from adenosine‐5′‐triphosphate (ATP).     

Sensing A Paradigm Shift in the Field of Molecular Recognition: From Selective to Differential Receptors

Molecular recognition has evolved from a science designed to understand biological systems into a much more diverse area of research. While work continues to elucidate “nature's tricks” with respect to intermolecular interactions, much attention has turned to the perspective that molecular recognition, by design, can lead to new technologies. Applications ranging from molecular sensing to information storage and even working molecular machines have been envisioned. This review will highlight a few historical hallmarks of molecular recognition oriented at studying the basic science of intermolecular interactions, but then detail recent advances in molecular recognition aimed towards applications in the field of molecular sensing. Rational design can be used to create synthetic receptors with a good deal of predictability and selectivity, and many signal transduction mechanisms exist for converting these receptors into sensors. This is the first topic discussed. The concept of “differential” or “generalized” sensing is then presented, where one uses an array of sensors that do not necessarily conform to the “lock and key” principle. This approach to sensing is inspired by the mammalian senses of taste and smell, which we briefly describe. To mimic senses of taste and smell, one is naturally led to the use of combinatorial libraries, a direction of research that has seen continued growth over the past few years. We summarize the current state of the art in synthetic combinatorial receptors/sensors, and then predict a future direction that the field of molecular recognition will possibly take. The review is not meant for the specialist, but instead for a general audience. It does not present a highly detailed analysis of each individual topic: synthetic receptors, sensors, olfaction/gustation, and combinatorial receptors/sensors. Instead, this review shows how all these fields complement each other and fit together to create sensing devices. Our conclusion is that specific analyte sensing, differential sensing, and combinatorial chemistry can and will be combined to create sensor arrays, and give the subfield of molecular recognition that uses synthetic systems a bright future in this type of sensing scenario.     

基于核酸分子识别的电化学分析方法与应用

核酸作为生物体遗传信息的载体以及分子生物学和生物分析化学中重要的功能分子,近年来在电化学分析中受到了越来越多的重视。本文以作者所在研究组的工作为实例,对核酸分子识别的电化学分析方法作出简要的评述,内容涉及核酸序列和基因变异的电化学分析以及核酸作为功能分子进行识别检测的电化学分析等等。     

Exploring New Molecular Architectures for Anion Recognition: Synthesis and ATP Binding Properties of New Cyclam‐Based Ditopic Polyammonium Receptors.

Synthesis and characterization of three new polyamine receptors, composed of a cyclam unit (cyclam=1,4,8,11‐tetraazacyclotetradecane) linked by a 2,6‐dimethylpyridinyl spacer to the linear polyamines 1,4,8,11‐tetraazaundecane ( L1py ), 1,4,7‐triazaheptane ( L2py ), and to a quaternary ammonium group ( L3 py⁺ ), are reported. All receptors form highly charged polyammonium cations at neutral pH, suitable for anion recognition studies. ATP recognition was analyzed by using potentiometric, calorimetric, ¹H and ³¹P NMR measurements in aqueous solution. All receptors form 1:1 adducts with ATP in aqueous solution, stabilized by charge–charge and hydrogen‐bonding interactions between their ammonium groups and the anionic triphosphate chain of ATP. The binding ability of the three receptors for ATP increases in the order of L3 py⁺ < L2py < L1py . These adducts are stabilized by largely favourable entropic contributions, probably due to the large desolvation of the host and guest species upon complexation. The sequence observed for the binding affinity is explained in terms of the different ability of the three receptors to wrap around the phosphate chain of ATP.     

锁核酸分子信标在分子识别与生物分析中的应用

分子信标是一种荧光探针,闭合时呈发夹结构。其5'末端修饰荧光基团,3'末端修饰猝灭基团。当目标存在时,环部与目标结合,发夹打开,发出荧光。锁核酸是一类双环状寡核苷酸衍生物,能够遵循碱基互补配对原则与核酸结合。锁核酸分子信标技术,结合了分子信标无需分离未结合探针而直接检测的优势和锁核酸亲合力强、热稳定性好、抗酶切以及体内无毒等特点,在核酸检测方面具有灵敏度高、特异性好的独特优势,近年来得到广泛关注。本文介绍了锁核酸修饰分子信标的结构、功能、设计要点,及其研究现状和一些重要进展,并讨论了目前锁核酸分子信标在分子识别及生物分析中的应用及存在的问题和发展前景。     

化学生物学中识别与组装的若干问题

化学与生物学的交叉与融合产生了新学科——化学生物学,开拓了化学和生物学研究的新领域,使人类得以从分子水平来阐释生命过程,揭示生命的奥秘。分子识别和组装是体系的构筑与功能集成的基础,也是自然界生物进行信息存贮、复制和传递的基础,以此来研究构筑具有特定生物学功能的超分子体系,对揭示生命现象和过程具有重要意义。本文结合我们的研究工作从（1）谷胱甘肽过氧化物酶(GPX)模拟与底物识别;（2）医用再生材料与活性支架;（3）类病毒颗粒的组装与解组装3个方面讨论了化学生物学中的识别与组装的意义。     

L-精氨酸盐酸盐/磷脂酰胆碱脂质体的制备及其对ATP的分子识别

用L-精氨酸盐酸盐和磷脂酰胆碱制备了L-广精氨酸盐酸盐／磷脂酰胆碱脂质体受体,研究了受体与腺苷三磷酸(ATP)在脂质体亲脂区通过分子间氢键进行的分子识别。透射电镜表征发现脂质体呈明显的双层膜圆球形,粒径100-200mm;并对氢键识别作用进行了UV-Vis光谱研究。