Enterovirus Inhibition by Hinged Aromatic Compounds with Polynuclei.

The modern world has no available drugs for the treatment of enteroviruses (EV), which affect millions of people worldwide each year. The EV71 is a major causative disease for hand, foot, and mouth disease; sometimes it is associated with severe central nervous system diseases. Treatment for enteroviral infection is mainly supportive; treatment for aseptic meningitis caused by enteroviruses is also generally symptomatic. Upon the urgent request of new anti-enterovirus drugs, a series of hinged aromatic compounds with polynulei were synthesized through two different chemical pathways. Among these morpholine-furan/thiophene/pyrrole-benzene-pyrazole conjugates, three new agents exhibited inhibitory activity with EC50 = 2.29-6.16 µM toward EV71 strain BrCr in RD cells. Their selectivity index values were reached as high as 33.4. Their structure-activity relationship was deduced that a thiophene derivative with morpholine and trifluorobenzene rings showed the greatest antiviral activity, with EC50 = 2.29 µM.

Targeted Paclitaxel by conjugation to iron oxide and gold nanoparticles.

The Fe(3)O(4) nanoparticles, tailored with maleimidyl 3-succinimidopropionate ligands, were conjugated with paclitaxel molecules that were attached with a poly(ethylene glycol) (PEG) spacer through a phosphodiester moiety at the (C-2')-OH position. The average number of paclitaxel molecules/nanoparticles was determined as 83. These nanoparticles liberated paclitaxel molecules upon exposure to phosphodiesterase.

Gold-nanostructured immunosensor for the electrochemical sensing of biotin based on liposomal competitive assay.

This work describes the development of a cost-effective, easy-to-use, portable immunoanalytical platform technology with sufficient sensitivity for use in the detection of physiologically important targets. Biotin, also known as vitamin H, was selected as the model analyte. The detecting system employs biotin-tagged, potassium ferrocyanide-encapsulated liposomes as the signal amplifier and PAH (poly allylamine hydrochloride)-modified, nanosized-Au particles assembled screen-printed electrode (nanoAu-SPE) as the working electrode. The diagnostic procedures are based on selective immunoanalytical recognitions and sensitive electrochemical detection. The model analyte biotin was determined based on a "competitive-type" immunoassay in which competition occurs between the analyte biotin and potassium ferrocyanide-encapsulated, biotin-tagged liposomes for a limited number of anti-biotin antibody binding sites, which were immobilized on the PAH/nanoAu/SPE surface. The nanostructured Au SPE surface was covalently bonded to the PAH layer, which subsequently interacted with anti-biotin antibodies. The ferrocyanide released from ruptured bound-liposomes was finally measured using square-wave voltammetry. The calibration curve for biotin had a linear range of 10(-11)-10(-2) M, covering nine orders of magnitude. The detection limit of this immunodetecting system was as low as 9.1 pg of biotin (equivalent to 4.5/microL of 8.3 x 10(-9) M).

Influence of ions, hydration, and the transcriptional inhibitor P4N on the conformations of the Sp1 binding site.

Three crystal structures containing the entire Sp1 consensus sequence d(GGGGCGGGG) with two or three additional base-pairs on either the 5' or 3' ends and overhangs have been determined. Despite the different lengths of DNA in the pseudo-dodecamers and pseudo-tridecamer, all three structures form A-DNA duplexes that share a common set of crystal contacts, including a T*(G.C) base triplet and a 5'-overhang that flips out and away from the helical axes to form a Hoogsteen base-pair with the 3'-overhang of a symmetry mate. The global conformations of the three structures differ, however, in the widths of their respective major grooves, the lengths of the molecules, and the extent of crystal packing. The structures were determined from crystals grown in an unusual precipitant for A-DNA, polyethylene glycol (PEG) 400, in combination with polyamines or ions; cobalt hexamine for the pseudo-tridecamer, and spermidine for the pseudo-dodecamers. As the Sp1 binding site is a target for antiviral and anticancer drugs, pseudo-dodecamer crystals were soaked with one such antiviral and anticancer compound, P4N. Although P4N was not visualized unambiguously in the electron density maps, the effect of the drug is evident from significant differences in the lattice constants, crystal packing, and overall conformation of the structure.

Liposome-based immunoaffinity chromatographic assay for the quantitation of immunoglobulin E in human serum.

Immunoglobulin E (IgE)-mediated type I allergies affect over 25% of the world's population; they are among the most common diseases in developed countries. Therefore, simple and rapid in vivo and in vitro methods for diagnosing allergies are becoming increasingly important. In this paper, we demonstrate the feasibility of using sulforhodamine B, a fluorescent dye, entrapped inside immunoliposomes, the outer surfaces of which were sensitized with IgE, as a signal amplifier for the development of a simple, rapid, and inexpensive colorimetric affinity chromatographic immunoassay for the detection of total IgE in serum. This assay operates based on competition between standards (or human serum samples) containing IgE and IgE-sensitized immunoliposomes for the limited number of antigen binding sites of immobilized anti-IgE antibodies at the antigen capture (AC) zone on the nitrocellulose membranes. The color density of the AC zone is indirectly proportional to the number of IgE units present in the test sample. The detection limit of this liposome-based immunoaffinity chromatographic assay was 0.37ng in IgE-free serum solution (equivalent to 20microL of a 18.5ngmL(-1) solution). A commercially available ELISA kit was used as a reference method to validate the proposed assay through the analysis of three human serum samples.

Facile preparation of self-assembled hydrogel-like GdPO4*H2O nanorods.

Of the methods employed in the preparation of one-dimensional lanthanide phosphate (LnPO(4)) nanorods/nanowires, such as GdPO(4), the hydrothermal method has been mainly used as a synthetic route. In this study, we report a facile low-temperature solution approach to prepare GdPO 4*H(2)O nanorods by simply refluxing GdCl(3) and KH(2)PO(4) for only 15 min at 88 degrees C, an approach that can easily be scaled up by increasing the reagent amounts. We observed a highly viscous macroscopic hydrogel-like material when we mixed as-prepared GdPO(4)*H(2)O nanomaterials with H(2)O. Hydrogels are an important class of biomaterials. Their building blocks, normally formed from protein-, peptide-, polymer-, and lipid-based materials, offer three-dimensional scaffolds for drug delivery, tissue engineering, and biosensors. Our preliminary results showed that GdPO(4)*H(2)O hydrogels could be used for encapsulation and drug release, and that they were biocompatible, acting as scaffolds to foster cell proliferation. These findings suggested that they might have biomedical uses. Our findings may lead to the creation of other inorganic nanomaterial-based hydrogels apart from the organic and biomolecular protein-, peptide-, polymer-, and lipid-based building blocks.

Water-dissolvable sodium sulfate nanowires as a versatile template for the fabrication of polyelectrolyte- and metal-based nanotubes.

This study presents the synthesis of water-dissolvable sodium sulfate nanowires, where Na(2)SO(4) nanowires were produced by an easy reflux process in an organic solvent, N,N-dimethylformamide (DMF) and formed from the coexistence of AgNO(3), SnCl(2), dodecylsodium sulfate (SDS), and cetyltrimethylammonium bromide (CTAB). Na(2)SO(4) nanowires were derived from SDS, and the morphology control of the Na(2)SO(4) nanowires was established by the cooperative effects of Sn and NO(3)(-), while CTAB served as the template and led to homogeneous nanowires with a smooth surface. Since the as-synthesized sodium sulfate nanowires are readily dissolved in water, these nanowires can be treated as soft templates for the fabrication of nanotubes by removing the Na(2)SO(4) core. This process is therefore significantly better than other reported methodologies to remove the templates under harsh condition. We have demonstrated the preparation of biocompatible polyelectrolyte (PE) nanotubes using a layer-by-layer (LbL) method on the Na(2)SO(4) nanowires and the formation of Au nanotubes by the self-assembly of Au nanoparticles. In both nanotube synthesis processes, PEI (polyethylenimine), PAA (poly(acrylic acid)), and Au nanoparticles served as the building blocks on the Na(2)SO(4) templates, which were then rinsed with water to remove the core templates. This unique water-dissolvable template is anticipated to bring about versatile and flexible downstream applications.