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1.
License to fuse! A phosphorylated fusion peptide can mediate membrane fusion when the phosphates (green triangles, see scheme) are removed by phosphatases (blue spheres), delivering the contents of the liposome into the cytosol. This phosphatase-triggered approach may be useful to create target-specific lipid nanocarriers.  相似文献   

2.
Synthetic anion transporters (SATs) of the general type (n-C18H37)2N-COCH2OCH2CO-(Gly)3-Pro-(Gly)3-O-n-C7H15, 1, are amphiphilic peptides that form anion-conducting pores in bilayer membranes. To better understand membrane insertion, assembly and aggregation dynamics, and membrane penetration, four novel fluorescent structures were prepared for use in both aqueous buffer and phospholipid bilayers. The fluorescent residues pyrene, indole, dansyl, and NBD were incorporated into 1 to give 2, 3, 4, and 5, respectively. Assembly of peptide amphiphiles in buffer was confirmed by monitoring changes in the pyrene monomer/excimer peaks observed for 2. Solvent-dependent fluorescence changes that were observed for indole (3) and dansyl (4) side-chained SATs in bilayers showed that these residues experienced an environment between epsilon=9 (CH2Cl2) and epsilon=24 (EtOH) in polarity. Fluorescence resonance energy transfer (FRET) between 2 and 3 demonstrated aggregation of SAT monomers within the bilayer. This self-assembly led to pore formation, which was detected as Cl(-) release from the liposomes. The results of acrylamide quenching of fluorescent SATs supported membrane insertion. Studies with NBD-labeled SAT 5 showed that peptide partition into the bilayer is relatively slow. Dithionite quenching of NBD-SATs suggests that the amphiphilic peptides are primarily in the bilayer's outer leaflet. Images obtained by using a fluorescence microscope revealed membrane localization of a fluorescent SAT. Taken together, this study helps define the insertion, membrane localization, and aggregation behavior of this family of synthetic anion transporters in liposomal bilayers.  相似文献   

3.
Although a lipid bilayer is only several nanometers in thickness, giant liposomes (GLs) make it possible to observe the dynamic features of individual membrane vesicles in real time with optical microscopy. Recent progress in GL preparation methods allows one to make reproducible image analyses of essential characteristics of membrane vesicles including fusion, division and poration processes. As a model of living cells, morphological changes of GLs that encapsulate cytoskeletal filaments such as microtubules or F-actin can be investigated directly. Applications of GLs based on the advantages of their large size is described using patch clamps, injection, mechanical transducer and so on.  相似文献   

4.
The need to decipher various biological events has led to the elucidation of the molecular mechanisms underlying a number of disease processes. Consequently, the detection and simultaneous monitoring of chemical interactions between biological targets has become indispensable in medical diagnosis, targeted therapeutics, and molecular biology. Multiplexed applications employing nanomaterials, which represent the integration of nanotechnology and biology, have changed the bioanalytical outlook and provided various promising tools. Among these nanomaterials, fluorescent dye-doped silica nanoparticles have demonstrated excellent potential for use in advanced bioanalysis to facilitate deeper understanding of biology and medicine at the molecular level. In particular, silica nanoparticles have been applied to diagnostics and therapeutic applications in cancer and gene/drug delivery. This feature article summarizes recent developments in the synthesis, biocompatibility, and bioapplications of fluorescent dye-doped silica nanoparticles.  相似文献   

5.
The colloidal dispersion stability of nano-sized graphene sheets in supercritical fluid (SCF) media is very important for developing SCF-based exfoliation and dispersion technologies for stabilization and solubilization of graphenes. We carried out molecular dynamics simulations to elucidate the stability mechanism of graphene in supercritical CO(2) (scCO(2)). The potential of mean force (PMF) between two graphene nanosheets in scCO(2) was simulated, and the effect of scCO(2) density and temperature on the PMF behavior has been investigated. The simulation results demonstrate that there exists a free energy barrier between graphenes in the scCO(2) fluid, possibly obstructing the aggregation of graphenes. The single-layer confined CO(2) molecules between the graphene sheets can induce a dominating repulsion interaction between graphene sheets. At higher scCO(2) fluid density, there are more confined CO(2) molecules within the interplate regions, resulting in a stronger repulsive free energy barrier. The effect of temperature on the PMF is relatively minor. The scCO(2) solvent structure shows layered confined arrangement in the interfacial region near the graphene nanosheets, which is correlated well with the PMF profile curve.  相似文献   

6.
Efforts towards using advanced computer graphics for improved visualization of three-dimensional (3-D) secondary ion mass spectrometry (SIMS) data are described. The application of the Visualization Toolkit (vtk), a freely available C++ class library for 3-D graphics and visualization for both PC and Unix systems, is demonstrated. Various available algorithms are used to analyze and visualize features otherwise hidden within data. A selection of examples is presented to demonstrate the capabilities of data visualization.  相似文献   

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We report the synthesis and preliminary characterization of "clickable" inhibitors of human transglutaminase 2 (TG2). These inhibitors possess the 3-halo-4,5-dihydroisoxazole warhead along with bioorthogonal groups such as azide or alkyne moieties that enable subsequent covalent modification with fluorophores. Their mechanism for inhibition of TG2 is based on halide displacement, resulting in the formation of a stable imino thioether. Inhibition assays against recombinant human TG2 revealed that some of the clickable inhibitors prepared in this study have comparable specificity as benchmark dihydroisoxazole inhibitors reported earlier. At low micromolar concentrations they completely inhibited transiently activated TG2 in a WI-38 fibroblast scratch assay and could subsequently be used to visualize the active enzyme in?situ. The potential use of these inhibitors to probe the role of TG2 in celiac sprue as well as other diseases is discussed.  相似文献   

9.
Antibodies targeting specific antigens are widely utilized in biological research to investigate protein interactions or to quantify target antigens. Here, we introduce antigen–antibody proximity labeling (AAPL), a novel method to map the antigen interaction sites as well as interactors of antibody-targeted proteins. As a proof of concept, AAPL was demonstrated using sodium/potassium transporting ATPase (ATP1A1) and epidermal growth factor receptor 2 (ERBB2)-specific antibodies that were modified with an Fe(iii) catalytic probe. Once bound to their target proteins, Fe(iii)-induced catalytic oxidation occurred in proximity of the antigen''s epitope. Oxidative proteomic analysis was then used to determine the degree of oxidation, the site of oxidation within the targeted antigen, and the interacting proteins that were in close proximity to the targeted antigen. An AAPL score was generated for each protein yielding the specificity of the oxidation and proximity of the interacting protein to the target antigen. As a final demonstration of its utility, the AAPL approach was applied to map the interactors of liver–intestine-cadherin (CDH17) in colon cancer cells.

Modified catalytic antibodies targeting specific antigens are employed to investigate protein interactions and antigen interaction sites.  相似文献   

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Cancer immune evasion is one of the hallmarks of carcinogenesis. Cancer cells employ multiple mechanisms to avoid immune recognition and suppress antitumor immune responses. Recently, accumulating evidence has indicated that immune-related pathways are epigenetically dysregulated in cancer. Most importantly, the epigenetic footprint of immune-related pathways is associated with the patient outcome, underscoring the crucial need to understand this process. In this review, we summarize the current evidence for epigenetic regulation of immune-related pathways in cancer and describe bioinformatics tools, informative visualization techniques, and resources to help decipher the cancer epigenome.Subject terms: Genetics research, Biomarkers  相似文献   

12.
In recent years a variety of chemical approaches have been developed for elucidating the molecular basis of biological processes in which glycans participate. The chemical technologies uncovered have greatly influenced the progress of glycomics research programs. This tutorial review highlights recent advances in chemical tools which have been developed and their applications in studies aimed at gaining a better understanding of the roles that glycans play in biological processes.  相似文献   

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Novel glycolipids, which contain 2 and 15 oligomaltose units and a phosphatidylethanolamine, were synthesized and characterized by FTIR and (1)H-NMR spectroscopies. The well-defined linear structure of the glycolipids was assured by an end-point conjugation strategy using selective oxidation of the reducing end groups of maltose oligosaccharides, followed by aminolysis with distearoylphosphatidylethanolamine. The intermediate acids react selectively with amines to form amide linkages, catalyzed by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide. Conformations of the glycolipids at the air-water interface were proposed based on the film balance measurements. The unique conformations of glycolipids at interfaces may offer advantages over traditional PEO-derived lipids in regard to their applications for sterically stabilizing liposomes. The glycolipids demonstrated the ability for sterically stabilizing liposome dispersions, as determined by turbidity measurements.  相似文献   

15.
New approaches for manufacturing and application of peptide arrays on planar surfaces are emerging, thereby opening advanced opportunities to probe the expression and function of the proteome. In complementing DNA and protein array analyses, peptide fragment screening directly addresses functional protein interaction sites, leading to a detailed insight into the discovered molecular recognition events, placing them in the context of the whole genome, and even allowing rapid determination of the chemical nature of these interactions. This information can then be transferred into powerful small peptide tools that interfere with these interactions in vivo and help to link targets with phenotypes. With the spreading of new peptide array tools, peptide screening will extend its impact on modern genome-driven molecular biology. This will advance the systematic discovery and validation of new pharmaceutical targets as well as the development of potent molecular diagnostics for medical and ecological monitoring.  相似文献   

16.
Proton relaxometric properties of unilamellar DPPC liposomes embedding an amphiphilic paramagnetic chelate (Gd-DTPA-BC(14)A) in both layers of the phospholipid membrane or only in the external one are compared. The results show that the membrane's water permeability is able to quench the effect of the paramagnetic complexes located in the internal layer of DPPC liposomes, leading thus to an apparent lower global relaxivity.  相似文献   

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Chemistry is an experimental science whose research subjects are often not directly available within the close dimensions of a time or space. To optimize a particular teaching process or research, it is necessary to visualize phenomena, processes, or objects. Consequently, visualization is significant to problem solving in research and teaching. Visualization is applicable in those situations when it is required to reduce the dimensions of experimental objects to given numbers and values accessible to direct experience. In educational practice, this is related to one of the following situations: (1) the experiment is too long or too short; (2) the dimensions of the examined object are too small or too large; (3) the environment of the experiment is not accessible; (4) the parameters of the experiment or its effects are not directly available to the observer's senses; (5) there is a need for multiple revisions of the experiment; (6) the experiment is difficult to arrange or revise effectively; (7) the experiment is dangerous; (8) the experiment is too expensive; etc. The presentation of models of physicochemical processes and phenomena, models of atoms and molecules, and mechanisms of reaction, as well as experimental data and their mathematical models, provides a basis for considering the formulation of correct conclusions. The appropriate choice of visualization algorithms is decisive of the effectiveness of theoretical analyses. The main aspect of visualization is obviously its application to teaching or research. Thus, the choice of techniques depends on whether it is used for recognition, explanation, memorization, inspiration, or motivation. In research, the importance as well as area of usefulness of three main categories of visualization have also been established. These categories are: illustration—relating to the presentation of an existing picture of object; representation—the presentation of an image assigned to an object; and visualization—related to the presentation of an image created for the object. Research work on preparing means for visualization confirms that, depending on the particular aspect of categorizing visualization, it may be useful, as well, to assign additional criteria such as dimensions, degree, functions, methodological contexts, experimental relationship, and medial effectiveness into visualization. In recent years, at the Institute of Chemical Education of Poznan's Adam Mickiewicz University such research was undertaken. Its main aim was to determine the educational effectiveness of different types of chemical visualizations. Methods for the visualization of chemical issues were developed and a series of original video and animation sequences presenting different aspects of chemical visualization prepared. Interactive Internet instructions sets were produced and methods of visualization categorized. Effectiveness in using different types of chemical visualizations was estimated. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002  相似文献   

20.
Hyperpolarization of cationic liposomes improves their stability in the presence of human serum albumin.  相似文献   

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