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Infection with Shiga toxin (Stx)-producing Escherichia coil O157:H7, which causes diarrhea and hemorrhagic colitis in humans, often results in fatal systemic complications, such as neurological damage and hemolytic-uremic syndrome. Because Stx circulating in the blood is a major causative factor of these complications, the development of a Stx neutralizer that functions in the circulation holds promise as a viable therapy. Here we developed a series of carbosilane dendrimers, in which trisaccharides of globotriaosyl ceramide, a receptor for Stx, were variously oriented at their termini (referred to as SUPER TWIG), and identified a SUPER TWIG with six trisaccharides as a Stx neutralizer functioning in the circulation. This SUPER TWIG specifically bound to Stx with high affinity ([K.sub.d] = 1.1 x [10.sup.-6] M) and inhibited the incorporation of the toxin into target cells. Intravenous administration of the SUPER TWIG along with Stx to mice substantially reduced the fatal brain damage and completely suppressed the lethal effect of Stx. Moreover, the SUPER TWIG protected mice from challenge with a fatal dose of E. coli O157:H7, even when administered after the establishment of the infection. The SUPER TWIG neutralized Stx in vivo by a mechanism in which the accumulation and immediate degradation of Stx by phagocytic macrophages present in the reticuloendothelial system were induced. Taken together, our findings indicate that this SUPER TWIG is therapeutic agent against infections by Stx-producing E. coli.

By doping 1,1-dimethyl-2,5-bis(N,N-dimethylaminophenyl)-3,4-diphenylsilole (silole-A) in poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT), an improved photoconductive characteristics was observed for a single layer organic device fabricated by a spin-coating process. A maximum external quantum efficiency (EQE) was 8.9% at -20 MV/m when the ratio of silole-A:F8BT was 75 mol%. The EQE of the reference device with F8BT only was 0.06%, and the highest EQE was approximately 160 times higher than that of the reference device. In addition, the photoluminescence (PL) quantum efficiency of the silole-A:F8BT neat film was lower than those of silole-A and F8BT neat films. The lower PL quantum efficiency indicates that the photo-induced carriers efficiently dislocate in the organic layer, resulting in the high EQE of organic photoconductive device. [ABSTRACT FROM AUTHOR]

Preparation of photo-responsive carbosilane dendrimers bearing 4-phenylazobenzonitrile units on their molecular surface has been accomplished, and their both photo and thermal behaviors have also been characterized. These functional dendrimers suggest that the apparent molecular sizes of the cis-isomers are smaller than those of the corresponding trans-isomers, since the molecular diameter of these dendrimers would be shorter on the basis of trans→cis photo-isomerization of azobenzene. [ABSTRACT FROM AUTHOR]

We have observed an electroluminescence (EL) of perylene (blue), coumarin 6 (green), 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran and/or zinc tetra-phenylporphyrin (red) via an efficient intermolecular energy transfer from poly (m-hexoxyphenyl)phenylsilane (PHPPS). The EL device has a single layer which was prepared simply by spin coating the mixed solution of PHPPS and energy-matched dye molecules. The EL spectrum can easily be tailored by intermixing appropriate dye molecules in the solution. We demonstrated a white EL from the mixture of PHPPS and these four dyes. The combination of a conducting polysilane and energy-matched dye molecules enabled us to open a field of Si-based EL devices through wet processes. [ABSTRACT FROM AUTHOR]

Poly[9,9-dioctylfluorenyl-2,7-diyl]-co-1,4-benzo-(2,1,3)-thiadiazole (F8BT) is one of the suitable materials for color-selective organic photoconductive devices owing to its high carrier mobility and absorption coefficient against only the blue light. We investigated a mixing method using a silole derivative, 1,1-dimethyl-2,3,4,5-tetraphenylsilole (DMTPS), in F8BT to improve the ratio between photocurrent and dark current (ON/OFF ratio), which is an important parameter for practical organic photoconductive devices. These organic materials can be coated by a solution process, which leads us to realize a low fabrication cost and a large device area in the future. By adding DMTPS into F8BT, the maximum improvement in ON/OFF ratio of 5 times was achieved compared with the reference device with F8BT only; however, the external quantum efficiency was independent of the concentration of DMTPS less than 50 wt %. In addition, the wavelength selectivity of DMTPS:F8BT in the visible wavelength region was almost the same as that of F8BT only. This result indicates that the DMTPS:F8BT layer can absorb only the blue light, indicating the possibility of a color separation without a prism for high-resolution cameras by combining the green- and red-sensitive devices. [ABSTRACT FROM AUTHOR]

New chiral dopants for nematic liquid crystals, containing a (S)-3,3′-(4H,4′H)-spirobi(2H-naphtho[1,2-b]pyran) skeleton, were synthesized and their helical twisting powers (HTP) were evaluated. A chiral dopant with two terphenyl structures showed the highest molar HTP value of 50.3 μm-1 mol-1 kg. [ABSTRACT FROM AUTHOR]

The synthesis and optical resolution of 3,3'-(4H,4'H)-spirobi(2H-naphtho[1,2-b]pyran)-6,6'-dicarboxylic acid were successfully accomplished. The formation of the spiro skeleton and the bromination of the aromatic ring were easily achieved in the presence of bromine. Optical resolution was achieved by amidation with L-valinol (2-amino-3-methyl-1-butanol). [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Sugar-amino acid hybrid monomers were prepared. • Assembly of the monomers was accomplished by radical polymerization. • Affinities of the polymers against Stxs were examined. • High cluster-type polymers showed higher affinity than low cluster-type polymers. Abstract Synthetic assembly of sugar moieties and amino acids in order to create "sugar-amino acid hybrid polymers" was accomplished by means of simple radical polymerization of carbohydrate monomers having an amino acid-modified polymerizable aglycon. Amines derived from globotriaoside and lactoside as glycoepitopes were condensed with known carbobenzyloxy derivatives, including Z-Gly, Z- l -Ala and Z-β-Ala, which had appropriate spacer ability and a chiral center to afford fully protected sugar-amino acid hybrid compounds in good yields. After deprotection followed by acryloylation, the water-soluble glycomonomers were polymerized with or without acrylamide in the presence of a radical initiator in water to give corresponding copolymers and homopolymers, which were shown by SEC analysis to have high molecular weights. Evaluation of the biological activities of the glycopolymers against Shiga toxins (Stxs) was carried out, and the results suggested that glycopolymers having highly clustered globotriaosyl residues had high affinity against Stx2 (K D = 2.7∼4.0 µM) even though other glycopolymers did not show any affinity or showed very weak binding affinity. When Stx1 was used for the same assay, all of the glycopolymers having globotriaosyl residues showed high affinity (K D = 0.30∼1.74 µM). Interestingly, couple of glycopolymers having lactosyl moieties had weaker binding affinity against Stx1. In addition, when cytotoxicity assays were carried out for both Stxs, glycopolymers having highly clustered globotriaosyl residues showed higher affinity than that of the copolymers, and only highly clustered-type glycopolymers displayed neutralization potency against Stx2. [ABSTRACT FROM AUTHOR]

Abstract: An efficient synthesis of sialyllactosamine (SiaLacNAc) clusters using carbosilanes as core scaffolds has been accomplished by means of chemical and enzymatic approaches. N-Acetyl-d-glucosamine (GlcNAc) clusters having O-glycosidic linkage or S-glycosidic linkage were chemically synthesized from known intermediates in high yields. The GlcNAc clusters were first used as substrates for β1,4 galactosyl transferase using UDP-galactose (UDP-Gal) as a sugar source to provide corresponding N-acetyllactosamine clusters. Further sugar elongation of the LacNAc clusters was demonstrated using α2,3 sialyl transferase and CMP-neuraminic acid (CMP-NANA) to yield the corresponding SiaLacNAc clusters. [ABSTRACT FROM AUTHOR]

Abstract: Synthetic construction of fucosyl chitobiose [GlcNAcβ1→4(Fucα1→3)GlcNAc] as an allergy-associated carbohydrate epitope was accomplished from three building blocks. The trisaccharidic unit was further transformed into a carbohydrate monomer and polymerization of the glycomonomer proceeded smoothly to provide a series of glycopolymers having various carbohydrate densities. In addition to the organic syntheses, biological evaluations of the glycomonomer and the polymers were carried out and sugar-clustering effects were observed. [Copyright &y& Elsevier]

Abstract: A new compound having a 2,3,4,5-tetraphenylsilole derivative on the center silicon of Dumbbell(1)6Gb3; Silole-Dumbbell(1)6Gb3 (1) was previously reported. It was found that 1 exhibited strongly increased fluorescence both in water and in a 96% acetone/water mixed solvent. The physical behavior of 1 in water and in the 96% acetone/water mixed solvent was investigated, and analyses including fluorescence quantum yields, dynamic-light-scattering (DLS), atomic-force-microscopy (AFM), and fluorescence microscopy were carried out. It was clarified that 1 dynamically formed different types of aggregates in water and in higher acetone concentrations to yield high aggregation-induced emission (AIE) effects due to the formation of micelle-like particles in water and inversion-type micelles in the acetone/water mixed solvent, respectively. [Copyright &y& Elsevier]

Abstract: A glycocluster peripherally functionalized with a lactose (Lac: Galβ1→4Glcβ1–) derivative possessing a silole moiety as a luminophore was synthesized. The photoluminescence spectrum of the glycocluster showed extremely strong emission at 474nm and the absolute quantum yield was estimated to be 92% in distilled water. The emission intensity was decreased by increasing the amount of peanut agglutinin (PNA), a lactose-binding lectin, and plots of the relative fluorescence intensity revealed a decline of 95% in emission intensity. Fluorescence quenching of the glycocluster upon mixing with PNA could be easily observed by the naked eye under UV irradiation, whereas no distinct change in fluorescence properties of the glycocluster was observed when wheat germ agglutinin (WGA) was employed. [Copyright &y& Elsevier]

Abstract: Glycomonomers of sialic acid in which the acetamide group at C-5 was converted into two kinds of Cbond substituents were prepared and the fully protected glycomonomers were directly polymerized before deprotection steps. Radical polymerization with acrylamide in DMF in the presence of ammonium persulfate and N,N,N’,N’-tetramethylethylenediamine proceeded smoothly and gave corresponding sialopolymers. Interestingly glycomonomers had hemagglutination inhibitory activities not only for H1N1 but also for H3N2 of human influenza virus strains. [Copyright &y& Elsevier]

Abstract: Synthetic construction of a Lex determinant was accomplished via slightly modified Gabriel amine synthesis from three building blocks. Further transformations followed by polymerization of the Lex derivative gave a glycopolymer having trisaccharidic units as pendant-type epitopes. [Copyright &y& Elsevier]

Abstract: A novel O-protected lactose (Galβ1→4Glcβ1–) derivative bearing trimethoxysilyl group at the aglycon was developed as a silane coupling agent. Reaction of the coupling agent with tris(2,2′-bipyridine)ruthenium (II) dichloride (Rubpy) doped silica particle gave a Rubpy-doped silica particle peripherally functionalized with O-protected lactose derivative. De-O-protection of the particle with aqueous ammonia provided lactose-coating Rubpy-doped silica particles, combining luminophor encapsulated in silica matrix and carbohydrate having lectin-recognition ability. Specific adhesion of fluorescein isothiocyanate-labeled peanut agglutinin (FITC-PNA) to the lactose-coating Rubpy-doped silica particles was confirmed by fluorescence microscopic analysis. [Copyright &y& Elsevier]

Abstract: An efficient synthesis of a series of carbosilane dendrimers uniformly functionalized with sialyl α(2→3) lactose (Neu5Acα(2→3)Galβ(1→4)Glcβ1→) moieties was accomplished. The results of a preliminary study on biological responses against influenza virus hemagglutinin, using the sialyl lactose clusters showed unique biological activities on the basis of the structure–activity relationship according to the carbosilane scaffolds. [Copyright &y& Elsevier]

Abstract: A conventional synthesis of α-thioglycoside of sialic acid as a glycomonomer was accomplished. Radical copolymerization of the glycomonomer with vinyl acetate proceeded smoothly to afford a new class of glycopolymers having thiosialoside residues, in which all protection was removed by a combination of transesterification and saponification to provide a water-soluble thiosialoside cluster. The results of a preliminary study on biological responses against influenza virus neuraminidases using the thiosialoside polymer as a candidate for a neuraminidase inhibitor showed that the glycopolymer has potent inhibitory activity against the neuraminidases. [Copyright &y& Elsevier]

Abstract: A novel glycocluster periphery functionalized by globotriaose (Galα1–4Galβ1–4Glcβ1–) possessing a silole moiety as a luminophor was synthesized. The photoluminescence spectrum of the glycocluster in pure water showed extremely strong emission at 475nm. Analogous intense emission of the silole dendrimer was also observed in a lower water fraction of water/acetone mixture. The water fraction of the silole dendrimer solution strongly affected the emission intensity; however, these luminescences were constantly detected at around 475nm. [Copyright &y& Elsevier]

Abstract: An efficient synthesis of a series of carbosilane dendrimers uniformly functionalized with α-thioglycoside of sialic acid was accomplished. The results of a preliminary study on biological responses against influenza virus sialidases using thiosialoside clusters showed that some of the glycodendrimers have inhibitory potencies against the sialidases. [Copyright &y& Elsevier]

A novel anomeric β-thioacetate of an N-acetyllactosamine derivative was efficiently synthesized in high yield from the known 2-azido glycosyl chloride using thioacetic acid as a convenient reagent. The synthesis involved not only an SN2 replacement of the chloride by a carbothiolate anion but also a reductive acetamidation of the azide group. Applications of the thioacetate for glycosidation were demonstrated to provide both O- and S-glycosides in high yields. Furthermore, both intermediates gave a new class of glycoclusters that included thioglycosidic linkages. [Copyright &y& Elsevier]

[Display omitted] • One-pot reaction by means of Birch reduction followed by Williamson ether synthesis, for thiobenzylated CD and iodo-trehalose proceeded efficiently. • CD dimer linked through a trehalose moiety was synthesized. • Inclusion properties of the CD-dimer were carried out. • The CD-dimer is able to includes one TNS molecule. Synthetic assembly of two β-cyclodextrins (CDs) was efficiently accomplished using a 6,6′-di-iodotrehalose derivative as a unique linker by means of a one-pot reaction in liquid ammonia for Birch reduction and subsequent S N 2 replacement. The unique sulfide-linked CD dimer displayed a wider hydrophobic region due to the cavity of the CDs and a part of similar structure of a trehalose linker. An inclusion property of the CD dimer was tentatively examined using TNS (2-p-toluidinylnaphthalene-6-sulfonate) as a model guest compound. [ABSTRACT FROM AUTHOR]

Abstract: A carbosilane dendrimer (4a) and its silacyclopentadiene analog (4b), both functionalized with lactoses, were tested for their abilities to act as drug-delivery systems. The critical micelle concentrations of 4a and 4b were measured using the drop-volume method in water and were 1.7 and 2.9μM, respectively, suggesting that they could act as aggregates of glycoclusters. The amounts of the hydrophobic dye Orange OT loaded onto aqueous micelles of 4a and 4b and the stabilities of the dye/micelle complexes were determined by extracting the dyes from the complexes into chloroform. The particle sizes were measured for the loaded micelles by dynamic light scattering. Transfer of the dye from the micelles to peanut agglutinin was observed by fluorescence microscopy. Given the abilities of micelles of 4a and 4b to bind and release Orange OT, these glycocluster micelles may find use as drug-delivery systems. [Copyright &y& Elsevier]

Abstract: Synthesis of bi-fluorescence-labeled maltooligosaccharides for amylase assay was accomplished. Preliminary biological evaluation of both bi-fluorescence-labeled maltohexasaccharide and maltose using α-amylase was carried out, and the hexaosyl derivative showed unique variation on the basis of fluorescence resonance energy transfer (FRET). [Copyright &y& Elsevier]