Self‐Assembled Nanogel of Hydrophobized Dendritic Dextrin for Protein Delivery

Highly branched cyclic dextrin derivatives (CH‐CDex) that are partly substituted with cholesterol groups have been synthesized. The CH‐CDex forms monodisperse and stable nanogels with a hydrodynamic radii of ≈10 nm by the self‐assembly of 4–6 CH‐CDex macromolecules in water. The CH‐CDex nanogels spontaneously trap 10–16 molecules of fluorescein isothiocyanate‐labeled insulin (FITC‐Ins). The complex shows high colloidal stability: no dissociation of trapped insulin is observed after at least 1 month in phosphate buffer (0.1 M , pH 8.0). In the presence of bovine serum albumin (BSA, 50 mg · mL^?1), which is a model blood system, the FITC‐Ins trapped in the nanogels is continuously released (≈20% at 12 h) without burst release. The high‐density nanogel structure derived from the highly branched CDex significantly affects the stability of the nanogel–protein complex.

     

Injectable Hydrogel for Sustained Protein Release by Salt‐Induced Association of Hyaluronic Acid Nanogel

A hyaluronic acid‐based anionic nanogel formed by self‐assembly of cholesteryl‐group‐bearing HA is designed for protein delivery. The HA nanogel spontaneously binds various types of proteins without denaturation, such as recombinant human growth hormone, erythropoietin, exendin‐4, and lysozyme. The HA nanogel shows unique colloidal properties, in particular that an injectable hydrogel is formed by salt‐induced association of the HA nanogel. A pharmacokinetic study in rats shows that an in situ gel formulation, prepared by simply mixing rhGH and HA nanogel in phosphate buffer, maintains plasma rhGH levels within a narrow range over one week. Therefore, HA nanogels offer a simple method for easy formulation of therapeutic proteins and are effective for sustained protein release systems.

     

Galois extensions,plus closure,and maps on local cohomology

Given a local domain $(R,\mathfrak{m})$ of prime characteristic that is a homomorphic image of a Gorenstein ring, Huneke and Lyubeznik proved that there exists a module-finite extension domain S such that the induced map on local cohomology modules $H_{\mathfrak{m}}^i(R)\to H_{\mathfrak{m}}^i(S)$ is zero for each $i<\dim R$. We prove that the extension S may be chosen to be generically Galois, and analyze the Galois groups that arise.     

Single-component nanodiscs via the thermal folding of amphiphilic graft copolymers with the adjusted flexibility of the main chain

Nanodiscs have attracted considerable attention as structural scaffolds for membrane-protein research and as biomaterials in e.g. drug-delivery systems. However, conventional disc-fabrication methods are usually laborious, and disc fabrication via the self-assembly of amphiphiles is difficult. Herein, we report the formation of polymer nanodiscs based on the self-assembly of amphiphilic graft copolymers by adjusting the persistence length of the main chain. Amphiphilic graft copolymers with a series of different main-chain persistence lengths were prepared and these formed, depending on the persistence length, either rods, discs, or vesicles. Notably, polymer nanodiscs were formed upon heating a chilled polymer solution without the need for any additives, and the thus obtained nanodiscs were used to solubilize a membrane protein during cell-free protein synthesis. Given the simplicity of this disc-fabrication method and the ability of these discs to solubilize membrane proteins, this study considerably expands the fundamental and practical scope of graft-copolymer nanodiscs and demonstrates their utility as tools for studying the structure and function of membrane proteins.

A strategy for the fabrication of nanodiscs via the self-assembly of thermoresponsive amphiphilic graft copolymers is demonstrated.     

5,11-Diazadibenzo[hi,qr]tetracene: Synthesis,Properties, and Reactivity toward Nucleophilic Reagents

5,11-Diazadibenzo[hi,qr]tetracene was synthesized as a new nitrogen-substituted polycyclic heteroaromatic compound by Pd-catalyzed cycloisomerization of an alkyne precursor followed by oxidative cyclization with bis(trifluoroacetoxy)iodobenzene. The substitution of imine-type nitrogen atoms significantly enhanced its electron-accepting character and facilitated the direct nucleophilic addition of arylamines under strongly basic conditions to afford the desired amino-substituted products. The introduction of amino groups induced a remarkable red-shift in their absorption spectra; the tetrasubstituted product exhibited intense near-infrared absorbing property. Furthermore, the π-electronic system, which includes a redox-active 1,4-diazabutadiene moiety, underwent reversible interconversion to its corresponding reduced form upon reduction with NaBH₄ and aerobic oxidation.     

Two New Syntheses of the Pyranojuglone Pigment α-Caryopterone

By a simple process, 3-methoxyjuglone (= 8-hydroxy-2-methoxy-1,4-naphthoquinone; 9 ) has been synthesized from 1,2,4-trimethoxybenzene ( 5 ) and converted, after prenylation, to α-caryopterone ( 1 ; Scheme 1), a pyranojuglone pigment from Caryopteris clandonensis. On the other hand, juglone (= 5-hydroxy-1,4-naphthoquinone; 12 ) was regioselectively prenylated at C(2) via its 1-methoxy-cyclohexa-1,3-diene adduct 15 (Scheme 2). The 2-prenyljuglone ( 4 ) thus formed led to 1 after oxidation and other reactions.     

An enzyme electrode based on electromagnetic entrapment of the biocatalyst bound to magnetic beads

A new type of biosensor is described. It is based on the use of a Clark-type oxygen electrode placed in an electromagnetic field. The biomolecules used in this sensor are immobilized on small magnetic beads which are added to the system when needed and removed as required. By varying the strength of the magnetic field, a homogeneous distribution of particles at the electrode tip is achieved. The electrode is used for the determination of glucose with immobilized glucose oxidase as well as cells of Saccharomyces cerevisiae.     

Preparation of benzolactams by Pd(OAc)2-catalyzed direct aromatic carbonylation

We developed a new method for Pd(II)-catalyzed direct aromatic carbonylation in a phosphine-free catalytic system using Pd(OAc)2 and Cu(OAc)2 in an atmosphere of CO gas containing air. The carbonylation proceeded with ortho-palladation, inducing a remarkable site selectivity to afford a variety of five- or six-membered benzolactams from secondary omega-arylalkylamines, such as N-alkylbenzylamines or N-alkylphenethylamines.     

Atomic emission spectrometric analysis of airborne particulate matter by direct nebulization of suspensions into the inductively-coupled plasma

A method is described for the rapid, direct emission spectrometric determination of iron in airborne particulate matter collected on polystyrene fiber filters using a conventional high-volume sampler and a Japanese low-volume sampler. The suspension prepared by dissolving the filter material in xylene was directly nebulized into the inductivelycoupled plasma excitation source. An ultrasonic immersion device was used for stirring purposes. Particles within the size range 0.1–100 μm in diameter are collected on the high-volume filters, while the largest particles on low-volume filters do not exceed 10 μm in diameter. The difference in the particle size composition entailed the use of a separate set of standard suspensions for each sample type. Standard suspensions for calibration were prepared from NBS SRM-1648 (urban particulates) as originally received and from its ground powder for high-volume and low-volume samples, respectively. The relative standard deviation was usually below 5%, which is acceptable for large-scale air pollution survey work. The possibility of determining other major and minor elements in airborne particulate matter was also examined.