Steric-control for the enantioselective hydrolysis of amino acid esters in hybrid membrane systems

The enantioselective hydrolysis of the amino acid esters, p-nitrophenyl-N-dodecanoyl-D(L)-phenylalaninates (C(12)-D(L)-Phe-PNP) catalyzed by active tripeptide, N-(benzyloxycarbonyl)-L-phenylalanyl-L-histidyl-L-leucine (Z-PheHisLeu) in the presence of coaggregates (hybrid membranes) composed of native phospholipid, L-alpha-dimyristoylphosphatidylcholine (DMPC) and nonionic surfactant, polyoxyethylene (8) lauryl ether (C(12)(EO)(8)) was easily controlled by regulating the reaction temperature and changing the composition of coaggregates. Furthermore, excellent correlations were observed between the enantioselectivity in the hydrolysis of C(12)-D(L)-Phe-PNP catalyzed by Z-PheHisLeu in the presence of coaggregates and physical properties of hybrid membranes. It is assumed that catalytic activities of tripeptide catalyst in hybrid membranes should be regulated by changing the microenvironments of reaction fields.     

High dispersion and fluorescence of anthracene doped in polyphenylsiloxane films

Phenylsilsesquioxane-diphenylsiloxane glass thick films doped with anthracene were prepared from homogeneous coating sols obtained from two different approaches. One approach consisted in incorporating the dye during the glass preparation (which implies the incorporation of the dye in an aqueous media). The doped-glass was further dissolved in the solvents mixture composed of cyclohexane and acetone. The other approach which is non-aqueous consisted simply in dissolving directly the preformed non-doped polyphenylsiloxane glass in the dye solutions. The stability of the organic-inorganic hybrid glass matrix in most organic solvents makes possible the incorporation of the dye without problems of miscibility and dispersion in the hybrid matrix. The coating was performed at room temperature using spin-coating technique prior to further heat-treatment. Crack-free and homogeneous films of high optical quality were obtained. The optical properties of the doped films based on their absorption and emission spectra were discussed owing the incorporation route of the dye. The results showed that the non-aqueous approach used to incorporate the dye minimizes the dye aggregation. This property associated to the preparation route permits to obtain optically active hybrid films loaded with high concentrations of anthracene (in the order of 10⁻² M) which enhance the fluorescence of the doped films. The hybrid doped-films obtained represent therefore a tremendous potential for applications in the field of optics and photonics including the development of new nonlinear optical materials. Bouzid Menaa and Masahide Takahashi both the author contributed equally.     

Ezrin Modulates the Cell Surface Expression of Programmed Cell Death Ligand-1 in Human Cervical Adenocarcinoma Cells

Cancer cells employ programmed cell death ligand-1 (PD-L1), an immune checkpoint protein that binds to programmed cell death-1 (PD-1) and is highly expressed in various cancers, including cervical carcinoma, to abolish T-cell-mediated immunosurveillance. Despite a key role of PD-L1 in various cancer cell types, the regulatory mechanism for PD-L1 expression is largely unknown. Understanding this mechanism could provide a novel strategy for cervical cancer therapy. Here, we investigated the influence of ezrin/radixin/moesin (ERM) family scaffold proteins, crosslinking the actin cytoskeleton and certain plasma membrane proteins, on the expression of PD-L1 in HeLa cells. Our results showed that all proteins were expressed at mRNA and protein levels and that all ERM proteins were highly colocalized with PD-L1 in the plasma membrane. Interestingly, immunoprecipitation assay results demonstrated that PD-L1 interacted with ERM as well as actin cytoskeleton proteins. Furthermore, gene silencing of ezrin, but not radixin and moesin, remarkably decreased the protein expression of PD-L1 without affecting its mRNA expression. In conclusion, ezrin may function as a scaffold protein for PD-L1; regulate PD-L1 protein expression, possibly via post-translational modification in HeLa cells; and serve as a potential therapeutic target for cervical cancer, improving the current immune checkpoint blockade therapy.     

Tocopheryl Phosphate Inhibits Rheumatoid Arthritis-Related Gene Expression In Vitro and Ameliorates Arthritic Symptoms in Mice

Anti-rheumatoid arthritis (RA) effects of α-tocopherol (α-T) have been shown in human patients in a double-blind trial. However, the effects of α-T and its derivatives on fibroblast-like synoviocytes (FLS) during the pathogenesis of RA remain unclear. In the present study, we compared the expression levels of genes related to RA progression in FLS treated with α-T, succinic ester of α-T (TS), and phosphate ester of α-T (TP), as determined via RT-PCR. The mRNA levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), matrix metalloproteinase (MMP)-3, and MMP-13 were reduced by treatment with TP without cytotoxicity, while α-T and TS did not show such effects. Furthermore, intraperitoneal injection of TP ameliorated the edema of the foot and joint and improved the arthritis score in laminarin-induced RA model mice. Therefore, TP exerted anti-RA effects through by inhibiting RA-related gene expression.     

Ligand effects on ESR and optical properties of gold atoms in gamma irradiated organic solid solutions at 77 K

Ligand effects on ESR and optical properties of Au0 atoms produced at 77 K in gamma irradiated solid solutions of AuCl/MTHF and AuCl/EtOH with and without HCl were investigated. Four groups of ESR lines were observed at 73 K more clearly around the magnetic fields at about 250, 280, 340, and 400 mT for both gamma irradiated MTHF and EtOH solid solutions with HCl than those without HCl. The values of a and g(J) calculated by Breit-Rabi analysis showed a remarkable dependence on the solvent polarity. It was confirmed that the signals were the hyperfine quartet corresponding to the transitions between the Zeeman levels of Au0 atoms with nuclear spin of 3/2 in the ground state, 2S(1/2). It was also confirmed that Au0 atoms produced after gamma irradiation were located in the nuclear environment of isotropic interaction with surrounding ligand molecules. Delocalization of the unpaired spin density of Au0 onto ligands is found to be as large as one in the case of Cu0 atoms. Our previous hypothesis of the occurrence of configuration mixing of d valence orbital into the wave function of the atom in its 2S(1/2) was strongly supported. The dependence of the ESR, optical absorption, and the steady-state emission and excitation characteristics on solvent polarity was cleared in this study. We observed two kinds of emissions i.e., a band at 385 nm and a set of emission bands at 456, 482, 484, and 520 nm. These correspond to two bands out of the six kinds of emissions observed previously. The bands were attributed to exciplex (Au0 x Ln...Au+)* and the excited Au0 atoms trapped in a large cavity, respectively. The negative counterion of Au+ of the gold compound plays an important role for the formation of the exciplexes.     

Substituent effect on the formation of organically-modified silicate-phosphate alternating copolymer through nonaqueous acid–base reaction

Organically-modified silicate-phosphate and silicate-phosphite copolymers were prepared through nonaqueous acid–base reaction. The inductive effect of the organic substituent of the starting materials such as organically-modified chlorosilane and phosphorous acid on the acid–base reaction was investigated by ³¹P NMR measurement and ab initio molecular orbital calculation. The condensation reaction takes place by nucleophilic addition of phosphate ion (or phosphite ion) to chlorosilane through S_N2 mechanism to form silicate-phosphate (or phosphite) network. The reactivity of the acid–base pair can be controlled by changing the inductive effect of the organic substituents on the starting materials.     

Well‐Defined Amphiphilic C60‐PEG Conjugates: Water‐Soluble and Thermoresponsive Materials

For the preparation of well‐defined H₂O‐soluble C₆₀ polymers, several C₆₀‐PEG conjugates were prepared from a C₆₀ biscarboxylic acid derivative and monodisperse NH₂‐PEGs (NH₂‐EG_n, n = 4 – 36) via amide conjugation. When the relatively long PEGs (EG_n, n ≥ 12) were employed, the C₆₀‐PEG conjugates became completely H₂O‐soluble by forming micelle‐like structure shown by the data of surface tension, DLS, and cryo‐TEM. Interestingly, these H₂O‐soluble C₆₀‐PEG conjugates (C₆₀(EG_n)₂, n = 12 – 36) showed reversible thermoresponse to form larger aggregates (ca. 1 μm by DLS) at higher temperatures. The temperature for the aggregation was related to the lengths of PEGs attached to C₆₀; 29 °C (C₆₀(EG_n)₂, n = 12), 51 °C (n = 20), and 72 °C (n = 36). This thermoresponse was speculated to occur by dehydration of well‐organized PEG chains in the micelle‐type structure of monodisperse C₆₀‐PEG caused by gauche‐to‐anti conformational change of PEG anchors. This thermoresponse of well‐defined amphiphilic C₆₀‐PEG conjugates indicates potential applications in areas such as temperature sensors and thermoresponsive materials.