Mimicking Chitin: Chemical Synthesis,Conformational Analysis,and Molecular Recognition of the β(1→3) N‐Acetylchitopentaose Analogue

Mimicking Nature by using synthetic molecules that resemble natural products may open avenues to key knowledge that is difficult to access by using substances from natural sources. In this context, a novel N‐acetylchitooligosaccharide analogue, β‐1,3‐N‐acetamido‐gluco‐pentasaccharide, has been designed and synthesized by using aminoglucose as the starting material. A phthalic group has been employed as the protecting group of the amine moiety, whereas a thioalkyl was used as the leaving group on the reducing end. The conformational properties of this new molecule have been explored and compared to those of the its chito analogue, with the β‐1,3 linkages, by a combined NMR spectroscopic/molecular modeling approach. Furthermore, the study of its molecular recognition properties towards two proteins, a lectin (wheat germ agglutinin) and one enzyme (a chitinase) have also been performed by using NMR spectroscopy and docking protocols. There are subtle differences in the conformational behavior of the mimetic versus the natural chitooligosaccharide, whereas this mimetic is still recognized by these two proteins and can act as a moderate inhibitor of chitin hydrolysis.     

Synthetic Glycopolypeptides as Potential Inhibitory Agents for Dendritic Cells and HIV‐1 Trafficking

Multivalent binding is a key for many critical biological processes and unique recognition and specificity in binding enables many of different glycans and proteins to work in a great harmony within the human body. In this study, the binding kinetics of synthetic glycopolypeptides to the dendritic cell lectin DC‐SIGN and their inhibition potential for DC‐SIGN interactions with the gp120 envelope glycoprotein of HIV‐1 (gp120) are investigated.

     

表面等离子体共振技术用于蛋白对氨基酸手性识别的动力学研究

利用SPR技术,以牛血清白蛋白和溶菌酶为探针构筑手性识别传感膜,开展了对L-和D-苯丙氨酸以及L-和D-色氨酸手性识别的动力学研究。实验结果表明,两种蛋白在与每种氨基酸分子的L-和D-型异构体相互作用过程都存在明显的动力学差异。动力学数据进一步显示两种蛋白与每种氨基酸L-型异构体的亲和力均大于D-型。     

1,1,3,3-四甲基胍基衍生物的合成及其与二酸的分子识别性能研究

四甲基胍分别与间苯二甲酰氯和间苯二磺酰氯反应合成了间苯二甲酰四甲基胍和间苯二磺酰四甲基胍,其结构经元素分析,IR,1H NMR和EI-MS表征.核磁滴定研究表明,上述化合物可与二酸形成1 ∶1化学计量络合物,其络合常数在5.33×105～3.68×105.     

Template‐Assembled Synthetic G‐Quadruplex (TASQ): A Useful System for Investigating the Interactions of Ligands with Constrained Quadruplex Topologies

A new biomolecular device for investigating the interactions of ligands with constrained DNA quadruplex topologies, using surface plasmon resonance (SPR), is reported. Biomolecular systems containing an intermolecular‐like G‐quadruplex motif 1 (parallel G‐quadruplex conformation), an intramolecular G‐quadruplex 2 , and a duplex DNA 3 have been designed and developed. The method is based on the concept of template‐assembled synthetic G‐quadruplex (TASQ), whereby quadruplex DNA structures are assembled on a template that allows precise control of the parallel G‐quadruplex conformation. Various known G‐quadruplex ligands have been used to investigate the affinities of ligands for intermolecular 1 and intramolecular 2 DNA quadruplexes. As anticipated, ligands displaying a π‐stacking binding mode showed a higher binding affinity for intermolecular‐like G‐quadruplexes 1 , whereas ligands with other binding modes (groove and/or loop binding) showed no significant difference in their binding affinities for the two quadruplexes 1 or 2 . In addition, the present method has also provided information about the selectivity of ligands for G‐quadruplex DNA over the duplex DNA. A numerical parameter, termed the G‐quadruplex binding mode index (G4‐BMI), has been introduced to express the difference in the affinities of ligands for intermolecular G‐quadruplex 1 against intramolecular G‐quadruplex 2 . The G‐quadruplex binding mode index (G4‐BMI) of a ligand is defined as follows: G4‐BMI=K_D^intra/K_D^inter, where K_D^intra is the dissociation constant for intramolecular G‐quadruplex 2 and K_D^inter is the dissociation constant for intermolecular G‐quadruplex 1 . In summary, the present work has demonstrated that the use of parallel‐constrained quadruplex topology provides more precise information about the binding modes of ligands.     

Minireview: Whole-cell,Nucleotide, and Enzyme Inhibition-based Biosensors for the Determination of Arsenic

Arsenic is a natural and highly toxic environmental contaminant and is intensely connected with human health. It can cause DNA damage, mutations, neurological disorders, and cancer. In previous few decades, large numbers of biosensors for recognition and identification of arsenic both qualitatively and quantitatively have been developed. The biosensor is a logical device that is usually used for identification of a particular or a group of analytes in samples. This review aims at various advancements made in the improvement of biosensors for arsenic detection such as whole cell-based, nucleotide-based, and enzyme inhibition-based biosensors. The review focuses on the technology used for development of arsenic biosensor along with their advantages and limitations.     

没食子酸磁性表面分子印迹聚合物的制备与选择性识别性能

羟基苯甲酸类化合物用途广泛,极性较强,在复杂水溶液体系中这些类似物的分离纯化与分析非常困难。 本文以磁性Fe₃O₄纳米颗粒为载体,没食子酸(GA)为模板分子,制备了磁性表面分子印迹聚合物(MIP)。 利用透射电子显微镜、红外光谱、磁强测定等检测手段对MIP进行了结构表征。 并对其吸附性能进行研究,比较了该MIP对GA及其它3种结构类似物的吸附性能差异。 结果表明,制备的以GA为模板的磁性分子印迹聚合物为核壳球形结构,键合牢固,对GA的吸附动力学符合准二级动力学方程模型,吸附过程属于Langmuir单分子层吸附。 该聚合物对GA表现出优异的选择性识别能力,其吸附量(318 K时37.736 mg/g)远远高于结构类似物。 该磁性分子印迹聚合物对模板分子不仅具有特异识别能力,而且能够磁控分离,分离效率高,可用于固相萃取。     

Naphthyridine‐Benzoazaquinolone: Evaluation of a Tricyclic System for the Binding to (CAG)n Repeat DNA and RNA

The expansion of CAG repeats in the human genome causes the neurological disorder Huntington's disease. The small‐molecule naphthyridine‐azaquinolone NA we reported earlier bound to the CAG/CAG motif in the hairpin structure of the CAG repeat DNA. In order to investigate and improve NA ‐binding to the CAG repeat DNA and RNA, we conducted systematic structure‐binding studies of NA to CAG repeats. Among the five new NA derivatives we synthesized, surface plasmon resonance (SPR) assay showed that all of the derivatives modified from amide linkages in NA to a carbamate linkage failed to bind to CAG repeat DNA and RNA. One derivative, NBzA , modified by incorporating an additional ring to the azaquinolone was found to bind to both d(CAG)₉ and r(CAG)₉. NBzA binding to d(CAG)₉ was similar to NA binding in terms of large changes in the SPR assay and circular dichroism (CD) as well as pairwise binding, as assessed by electron spray ionization time‐of‐flight (ESI‐TOF) mass spectrometry. For the binding to r(CAG)₉, both NA and NBzA showed stepwise binding in ESI‐TOF MS, and NBzA ‐binding to r(CAG)₉ induced more extensive conformational change than NA ‐binding. The tricyclic system in NBzA did not show significant effects on the binding, selectivity, and translation, but provides a large chemical space for further modification to gain higher affinity and selectivity. These studies revealed that the linker structure in NA and NBzA was suitable for the binding to CAG DNA and RNA, and that the tricyclic benzoazaquinolone did not interfere with the binding.     

Crystal Structure of 1:1 Complex of Honokiol and 1,4-Diazabicyclo[2.2.2]octane: Separation of Honokiol by Molecular Recognition

Phenomenon of molecular recognition between honokiol and 1,4-diazabicyclo[2.2.2]octane (DABCO) is discovered, and applied to separation of honokiol from extract of magnolia bark. Effects of material ratio on the yield and the purity were investigated. Honokiol (purity up to 97.3% and yield up to 83.9%) is obtained from Magnolia bark extract (honokiol 49.1%, magnolol 31.7%, others unknown 19.2%) on a favorable condition. The title complex, C₁₈H₁₈O₂·C₆H₁₂N₂, is characterized by IR and ¹HNMR and its crystal structure is determined by X-ray diffraction method. It crystallizes in monoclinic space group C2/c with a=38.860(3), b=9.205(3), c=12.588(4) Å, β=102.730(10)°, V=4392(2) ų, Z=8 and R=0.0500. Hinokiol molecules join to DABCO via O–H...N hydrogen bonds to form infinite chains. There are two symmetry independent DABCO molecules occupying in the crystal special positions of different point symmetries, C2 and Ci. Those located around the inversion center are disoredered as DABCO molecule is devoid of this symmetry element.     

Structural Optimization of Photoswitch Ligands for Surface Attachment of α‐Chymotrypsin and Regulation of Its Surface Binding

A modified gold surface that allows photoregulated binding of α‐chymotrypsin has previously been reported. Here the development of this surface is reported, through the synthesis of a series of trifluoromethyl ketones and α‐keto esters containing the azobenzene group and a surface attachment group as photoswitch inhibitors of α‐chymotrypsin. All of the compounds are inhibitors of the enzyme, with activity that can be modulated by photoisomerization. The best photoswitch shows a reversible change in IC₅₀ inhibition constant of >5.3 times on photoisomerization. The trifluoromethyl ketone 1 exhibited excellent photoswitching and was attached to a gold surface in a two‐step procedure involving an azide–alkyne cycloaddition. The resulting modified surface bound α‐chymotrypsin to a degree that could be modulated by UV/Vis irradiation, showing “slow‐tight” enzyme binding as observed for inhibitors in solution.     

Observation of a Quadrupole Surface Plasmon Mode for Au Nanorods: Effects of Surface Roughness and Crystal Facets

This paper describes how the surface roughness and synthetic methods of Au nanorods affect the optical properties that are often associated with localized surface plasmon resonances. We synthesized Au nanorods with different aspect ratios and surface roughness by using two different synthetic strategies to observe surface plasmon resonance bands. One set of nanorods was prepared in high yield by using a seed‐mediated dropwise‐addition method with a growth‐directing surfactant in aqueous solution (Au nanorods in aqueous phase, GNRA). The other set of Au nanorods were synthesized by the electrochemical deposition of Au onto an anodized aluminum oxide (AAO) template (Au nanorods by AAO template, GNRT). The length of the nanorods was controlled by changing the total charge that was passed through the cell and their diameter was monitored by changing the diameter of the template channel. The as‐prepared Au nanorods were optimized to observe a quadrupole mode, which is one of the higher‐order surface plasmon bands. Our results showed differences between the optical properties of GNRA and GNRT. The roughness and crystal structure of the Au nanorods affected their optical properties. Smooth and single‐crystal surface on GNRA had larger and sharper peaks than GNRT. The discrete dipole approximation (DDA) method was used to calculate the optical properties of the Au nanorods and these results were in good agreement with our experimental results.     

Fluorescent Probes for Selective Recognition of Hypobromous Acid: Achievements and Future Perspectives

Reactive oxygen species (ROS) have been implicated in numerous pathological processes and their homeostasis facilitates the dynamic balance of intracellular redox states. Among ROS, hypobromous acid (HOBr) has a high similarity to hypochlorous acid (HOCl) in both chemical and physical properties, whereas it has received relatively little attention. Meanwhile, selective recognition of endogenous HOBr suffers great challenges due to the fact that the concentration of this molecule is much lower than that of HOCl. Fluorescence-based detection systems have emerged as very important tools to monitor biomolecules in living cells and organisms owing to distinct advantages, particularly the temporal and spatial sampling for in vivo imaging applications. To date, the development of HOBr-specific fluorescent probes is still proceeding quite slowly, and the research related to this area has not been systematically summarized. In this review, we are the first to review the progress made so far in fluorescent probes for selective recognition and detection of HOBr. The molecular structures, sensing mechanisms, and their successful applications of these probes as bioimaging agents are discussed here in detail. Importantly, we hope this review will call for more attention to this rising field, and that this could stimulate new future achievements.     

Synthesis and Supramolecular Studies of Chiral Boronated Platinum(II) Complexes: Insights into the Molecular Recognition of Carboranes by β‐Cyclodextrin

The synthesis and characterisation of a novel isomeric family of closo‐carborane‐containing Pt^II complexes ((R/S)‐( 1 – 4 )?2 NO₃) are reported. Related complexes ( 5 ?NO₃ and 6 ?NO₃) that contain the 7,8‐nido‐carborane cluster were obtained from the selective deboronation of the 1,2‐closo‐carborane analogues. The corresponding water‐soluble supramolecular 1:1 host–guest β‐cyclodextrin (β‐CD) adducts ((R/S)‐( 1 – 4 ) ? β‐CD?2 NO₃) were also prepared and fully characterised. HR‐ESI‐MS experiments confirmed the presence of the host–guest adducts, and 2D‐¹H{¹¹B} ROESY NMR studies showed that the boron clusters enter the β‐CD from the side of the wider annulus. Isothermal titration calorimetry (ITC) experiments revealed enthalpically driven 1:1 and higher‐order supramolecular interactions between β‐CD and (R/S)‐( 1 – 4 )?2 NO₃ in aqueous solution. A comparison of the predominate 1:1 binding mode established that the affinity of β‐CD for the guest molecule is mainly influenced by the pyridyl ring substitution pattern and chirality of the host, whilst the nature of the closo‐carborane isomer also plays some role, with the most favourable structural features for β‐CD binding being the presence of the 4‐pyridyl ring, 1,12‐closo‐carborane, and an S configuration. The results reported here represent the first comprehensive calorimetric study of the supramolecular interactions between closo‐carborane compounds and β‐CD, and it provides fascinating insights into the structural features influencing the thermodynamics of this phenomenon.     

Generalization of multivariate optical computations as a method for improving the speed and precision of spectroscopic analyses

Multivariate optical computations (MOCs) offer improved analytical precision and increased speed of analysis via synchronous data collection and numerical computation with scanning spectroscopic systems. The improved precision originates in the redistribution of integration time from spurious channels to informative channels in an optimal manner for increasing the signal‐to‐noise ratio with multivariate analysis under the constraint of constant total analysis time. In this work, MOCs perform the multiplication and addition steps of spectral processing by adjusting the integration parameters of the optical detector or adjusting the scanning profile of the tunable optical filter. Improvement in the precision of analysis is achieved via the implicit optimization of the analytically useful signal‐to‐noise ratio. The speed improvements are realized through simpler data post‐processing, which reduces the computation time required after data collection. Alternatively, the analysis time may be significantly truncated while still seeing an improvement in the precision of analysis, relative to competing methods. Surface plasmon resonance (SPR) spectroscopic sensors and visible reflectance spectroscopic imaging were used as test beds for assessing the performance of MOCs. MOCs were shown to reduce the standard deviation of prediction by 15% compared to digital data collection and analysis with the SPR and up to 45% for the imaging applications. Similarly, a 30% decrease in the total analysis time was realized while still seeing precision improvements. Copyright © 2008 John Wiley & Sons, Ltd.     

Surface Plasmon Resonance Coupled with Potential‐step Chronoamperometry: Theory and Applications for Quantitative Measurements of Electrodeposited Thin Films

Cyclic voltammetry (CV) has been combined with surface plasmon resonance (SPR) for probing electrochemical deposition and redox‐initiated film reorganization and conformational changes. However, the varying potential during CV scans leads to unwanted SPR background changes and complicates interpretation of SPR signals. In this work, we show that, when SPR is coupled with CV, the background correction for underpotential deposition of copper and electropolymerization of aniline is either inaccurate or difficult to perform. For accurate thickness measurements of electrodeposited films, potential‐step (PS) chronoamperometry is a method of choice to combine with SPR. The theory that interprets double‐layer charging is used to explain the advantage of PS chronoamperometry over CV in quantifying the thickness of electrodeposited thin films. The influence of the double‐layer charging on the potential‐induced SPR signal change was analyzed, and the results were used to optimize experimental parameters for PS‐SPR. Overall, PS‐SPR is easier to operate, simpler in data interpretation, and more accurate for the film thickness measurement.     

Rim,Side Arms,and Cavity: Three Sites for the Recognition of Anions by Tetraazolium Resorcinarene Cavitands

Two tetrabenzoimidazolium‐resorcinarene cavitands were prepared and used for the recognition of chloride, bromide, iodide, cyanide, nitrate, perchlorate, hexanoate, benzenesulfonate, and p‐toluenesulfonate. Binding affinities of the two cavitands were determined by ¹H NMR titration and computational analysis. The observed spectral changes were related to specific interaction sites, which were supported by the computational studies. In the case of the C2?H tetrabenzoimidazolium‐resorcinarene, the recognition region of the inorganic anions and hexanoate was located at the rim of the cavitand, although chloride and bromide also interacted with the aromatic C?H bonds located between adjacent arms of the cavitand. By contrast, the recognition of the two anions with an aromatic ring (benzenesulfonate and p‐toluenesulfonate) results from encapsulation of the aromatic part of the anions inside the hydrophobic cavity of the host. In the case of the C2?Me tetrabenzoimizazolium‐resorcinarene receptor, the ability of the molecule to bind all inorganic anions and hexanoate was suppressed, but the receptor maintained its ability to strongly bind benzenesulfonate and p‐toluenesulfonate. This is interpreted in terms of suppression of the ability of the cavitand to form hydrogen bonds at the rim of the molecule due to replacement of the C2?H proton by a methyl group, while the hydrophobic pocket of the molecule maintains its binding abilities.     

Boronate‐Affinity Glycan‐Oriented Surface Imprinting: A New Strategy to Mimic Lectins for the Recognition of an Intact Glycoprotein and Its Characteristic Fragments

Lectins possess unique binding properties and are of particular value in molecular recognition. However, lectins suffer from several disadvantages, such as being hard to prepare and showing poor storage stability. Boronate‐affinity glycan‐oriented surface imprinting was developed as a new strategy for the preparation of lectin‐like molecularly imprinted polymers (MIPs). The prepared MIPs could specifically recognize an intact glycoprotein and its characteristic fragments, even within a complex sample matrix. Glycan‐imprinted MIPs could thus prove to be powerful tools for important applications such as proteomics, glycomics, and diagnostics.     

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.