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41.
Affinity capillary electrophoresis for the assessment of binding affinity of carbohydrate‐based cholera toxin inhibitors
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《Electrophoresis》2018,39(2):344-347
Developing tools for the study of protein carbohydrate interactions is an important goal in glycobiology. Cholera toxin inhibition is an interesting target in this context, as its inhibition may help to fight against cholera. For the study of novel ligands an affinity capillary electrophoresis (ACE) method was optimized and applied. The method uses unlabeled cholera toxin B‐subunit (CTB) and unlabeled carbohydrate ligands based on ganglioside GM1‐oligosaccharides (GM1os). In an optimized method at pH 4, adsorption of the protein to the capillary walls was prevented by a polybrene‐dextran sulfate‐polybrene coating. Different concentrations of the ligands were added to the BGE. CTB binding was observed by a mobility shift that could be used for dissociation constant (Kd) determination. The Kd values of two GM1 derivatives differed by close to an order of magnitude (600 ± 20 nM and 90 ± 50 nM) which was in good agreement with the differences in their reported nanomolar IC50 values of an ELISA‐type assay. Moreover, the selectivity of GM1os towards CTB was demonstrated using Influenza hemagglutinin (H5) as a binding competitor. The developed method can be an important platform for preclinical development of drugs targeting pathogen‐induced secretory diarrhea. 相似文献
42.
Cecily Eldridge Gracia Quek Michael Sako John H. Ryan Simon Saubern Mary Chebib James M. Macdonald 《Tetrahedron》2018,74(12):1245-1252
Four histrionicotoxin analogues were prepared in an efficient manner utilizing a nitrone dipolar cycloaddition reaction as the key step in forming tricyclic intermediate 13. The nitrile in intermediate 13 was reduced with DIBAL to an aldehyde which then underwent Z-selective Wittig reactions to produce intermediates containing the Z-alkene side-chain. Hydrogenation of the Z-alkenes produced saturated histrionicotoxin analogues whereas reduction with SmI2 afforded the unsaturated histrionicotoxin analogues. The histrionicotoxin analogues were shown to be potent non-competitive antagonists of the α4β2 and α7 nAChR's with the most potent analogue 3 displaying IC50's of 0.10 μM and 0.45 μM against the α4β2 and α7 nAChR's, respectively. The unsaturated analogues 15 and 18 displayed Hill slope (nH) of approximately 1 whilst the saturated analogues 16 and 3 had a nH of approximately 0.5, which may indicate that the saturated analogues are binding to more than one binding site. 相似文献
43.
U. Murali Krishna 《Tetrahedron letters》2004,45(2):257-259
Synthetic studies towards the diterpene natural product FCRR toxin have been undertaken. An intermolecular [5+2] oxidopyrylium-alkene cycloaddition reaction was employed to construct the 7-5-6 tricyclic framework. The reaction proceeded with very high regio- and stereoselectivity and the bridging ether was reductively cleaved to unmask the carbocycle. 相似文献
44.
Enhanced expression of B-subunit of Escherichia coli heat-labile enterotoxin in tobacco by optimization of coding sequence 总被引:2,自引:0,他引:2
Kang TJ Han SC Jang MO Kang KH Jang YS Yang MS 《Applied biochemistry and biotechnology》2004,117(3):175-187
Escherichia coli heat-labile toxin (LT) is a potent mucosal immunogen and immunoadjuvant for coadministered antigens. We synthesized a gene
encoding the B-subunit of LT(LTB) adapted to the coding sequence of tobacco plants and fused to the endoplasmic reticulum
retention signal SEKDEL to enhance its level of expression in plants. The synthetic LTB gene was cloned into a plant expression
vector adjacent to the CaMV 35S promoter and was introduced into tobacco by Agrobacterium-mediated transformation. The amount of LTB protein detected in transgenic tobacco leaves was 2.2% of the total soluble plant
protein, which is approx 200-fold higher than in previous reports of native LTB gene expression in transgenic plants. Enzyme-linked
immunosorbent assay indicated that plant-synthesized LTB protein bound specifically to GM1-ganglioside, suggesting that the LTB subunits formed active pentamers. 相似文献
46.
J. R. HENDERSON 《Molecular physics》2013,111(3):397-403
The statistical mechanics of fluids adsorbed on chemically patterned surfaces is far from straightforward when attempting to develop virial theorems for the interfacial free energy. This is because in general one would have to devise new procedures to distinguish surface tension from surface stress, even for wall-fluid models where the substrate atoms are replaced by an effective external field. However, the distinction may be made explicit for the special case of striped walls. This paper makes use of striped wall-fluid models to discuss the significance of fluid interfacial stress to patterned inhomogeneous fluids. In particular, it considers the adsorption of hemicylindrical drops on an array of high energy stripes. For the planar stripe geometry it is also possible to make effective use of the pressure tensor formalism. Beyond the special case of striped patterns it is not possible to use standard procedures based on virial theorems to directly evaluate interfacial free energy. The lessons learnt from these exercises apply especially to computer simulation studies of patterned inhomogeneous fluids. 相似文献
47.
A new signal amplification strategy based on mesoporous carbon-enriched palladium nanostructure (MSC-PdNS) was designed for enzyme-free electrochemical immunoassay of brevetoxin B (BTB) in marine toxins. The assay was carried out on a BTB-bovine serum albumin-functionalized electrode by using monoclonal mouse anti-BTB-labeling MSC-PdNS as the signal-transduction tag. A competitive-type assay protocol was successfully introduced to develop a high-efficiency enzyme-free immunoassay accompanying the doped palladium nanostructure into MSC-PdNS toward reduction of H2O2. Under the optimal conditions, the catalytic current decreased with the increment of BTB concentration in the range from 0.01 to 10 ng mL−1 with a detection limit (LOD) of 5.0 pg mL−1 BTB at the 3sblank criterion. The selectivity and precision were acceptable. In addition, the methodology was further validated for assaying spiked seafood samples, and consistent results between the electrochemical immunoassay and the referenced enzyme immunoassay were obtained. Importantly, the enzyme-free electrochemical immunoassay provides a promising approach for rapid screening of marine toxin because of its simplicity, low cost, sensitivity, specificity and without the need of sample pretreatment. 相似文献
48.
Bunyakul N Edwards KA Promptmas C Baeumner AJ 《Analytical and bioanalytical chemistry》2009,393(1):177-186
Fluorescence and electrochemical microfluidic biosensors were developed for the detection of cholera toxin subunit B (CTB)
as a model analyte. The microfluidic devices were made from polydimethylsiloxane (PDMS) using soft lithography from silicon
templates. The polymer channels were sealed with a glass plate and packaged in a polymethylmethacrylate housing that provided
leakproof sealing and a connection to a syringe pump. In the electrochemical format, an interdigitated ultramicroelectrode
array (IDUA) was patterned onto the glass slide using photolithography, gold evaporation and lift-off processes. For CTB recognition,
CTB-specific antibodies were immobilized onto superparamagnetic beads and ganglioside GM1 was incorporated into liposomes. The fluorescence dye sulforhodamine B (SRB) and the electroactive compounds potassium hexacyanoferrate
(II)/hexacyanoferrate (III) were used as detection markers that were encapsulated inside the liposomes for the fluorescence
and electrochemical detection formats, respectively. Initial optimization experiments were carried out by applying the superparamagnetic
beads in microtiter plate assays and SRB liposomes before they were transferred to the microfluidic systems. The limits of
detection (LoD) of both assay formats for CTB were found to be 6.6 and 1.0 ng mL−1 for the fluorescence and electrochemical formats, respectively. Changing the detection system was very easy, requiring only
the synthesis of different marker-encapsulating liposomes, as well as the exchange of the detection unit. It was found that,
in addition to a lower LoD, the electrochemical format assay showed advantages over the fluorescence format in terms of flexibility
and reliability of signal recording. 相似文献
49.
Bernardi A Arosio D Potenza D Sánchez-Medina I Mari S Cañada FJ Jiménez-Barbero J 《Chemistry (Weinheim an der Bergstrasse, Germany)》2004,10(18):4395-4406
The design and synthesis of two GM1 glycomimetics, 6 and 7, and analysis of their conformation in the free state and when complexed to cholera toxin is described. These compounds, which include an (R)-cyclohexyllactic acid and an (R)-phenyllactic acid fragment, respectively, display significant affinity for cholera toxin. A detailed NMR spectroscopy study of the toxin/glycomimetic complexes, assisted by molecular modeling techniques, has allowed their interactions with the toxin to be explained at the atomic level. It is shown that intramolecular van der Waals and CH-pi carbohydrate-aromatic interactions define the conformational properties of 7, which adopts a three-dimensional structure significantly preorganized for proper interaction with the toxin. The exploitation of this kind of sugar-aromatic interaction, which is very well described in the context of carbohydrate/protein complexes, may open new avenues for the rational design of sugar mimics. 相似文献
50.
In this paper, we investigate a model with yields: γ1 = A
1 + B
1
S
m
and γ2 = A
2 + B
2
S
n
, for the competition in the bioreactor of two competitors for a single nutrient, in which one of the competitors produces
toxin against its opponent. The existence of limit cycles in the 3-D system is obtained by using a Hopf bifurcation.
相似文献