Syntheses of aromatic polyketones and aromatic polyamide

High molecular weight aromatic polyketones were prepared from p- and m-phenoxybenzoic acid in polyphosphoric acid by heating the reaction mixture at 100°C. High molecular weight aromatic polyamide was derived from the polyketone obtained through Schmidt reaction or Beckmann rearrangement. The polyamide obtained by Schmidt reaction was found to have some regularity in an arrangement of its repeating units. The thermal stability of the polyketone and the polyamide were good.     

A practical solution for eliminating artificial image contrast in aberration-corrected TEM.

We propose a simple and practical solution to remove artificial contrast inhibiting direct interpretation of atomic arrangements in aberration-corrected TEM. The method is based on a combination of "image subtraction" for elimination of nonlinear components in images and newly improved "image deconvolution" for proper compensation of nonflat phase contrast transfer function. The efficiency of the method is shown by experimental and simulation data of typical materials such as gold, silicon, and magnesium oxide. The hypothetical results from further improvements of TEM instruments are also simulated. It is concluded that we can approach actual atomic structures by using the present method, that is, a proper combination of a Cs corrector, image subtraction, and image deconvolution processes.     

de novo design and synthesis of N-benzylanilines as new candidates for VEGFR tyrosine kinase inhibitors

N-Benzylanilines were designed and synthesized as vascular endothelial growth factor (VEGF)-2 inhibitors using de novo drug design systems based on the X-ray structure of VEGFR-2 kinase domain. Among compounds synthesized, compound showed the most potent inhibitory activity toward VEGFR-2 (KDR) tyrosine kinase and its IC(50) value was 0.57 microM.     

Synthesis and characterization of tetraanthroporphyrins

Linearly pi-expanded novel tetraanthroporphyrins with and without aromatic rings at the meso-positions were prepared quantitatively for the first time from the corresponding precursors by a retro-Diels-Alder reaction.     

Incubation type Si-based planar ion channel biosensor

A new planar-type ion channel biosensor with the function of cell culture has been fabricated using silicon on an insulator substrate as the sensor chip material. Coating of the sensor chip with fibronectin was essentially important for cell incubation on the chip. Although the seal resistance was quite low (∼7 MΩ) compared with the pipette patch-clamp gigaohm seal, the whole-cell channel current of the transient receptor potential vanilloid type 1 (TRPV1) channel expressing HEK293 cells was successfully observed, with a good signal-to-noise ratio, using capsaicin as a ligand molecule. Figure A new planer type ion channel biosensor with function of cell culture is fabricated using the silicon on insulator substrate as the sensor chip material. The coating of the sensor chip by the fibronectin was essentially important for the cell incubation on the chip. Whole cell channel current of TRPV1 channel was successfully observed using capsaicin as a ligand molecule with good signal to noise.     

Asymmetric thio-Michael/nucleophilic addition domino reaction with chiral N-sulfinimines

Optically active N-sulfinimines underwent stereoselective Michael/nucleophilic addition domino reaction triggered by magnesium thiolate to give alpha-phenylthiomethyl-beta-(N-sulfinylamino) esters in high diastereomeric excess. The adducts were readily converted into optically active alpha-methylene-beta-(N-sulfinylamino)esters so that this reaction provides a useful asymmetric aza-Baylis-Hillman-equivalent method.     

UV protection and singlet oxygen quenching activity of aloesaponarin I

The UV protection and singlet oxygen quenching of aloesaponarin I have been studied by means of laser spectroscopy. The excited-state intramolecular proton transfer that provides the UV protection takes place along only one of the molecule's two intramolecular hydrogen bonds, and this can be understood by considering the nodal pattern of the wave function. The functional groups participating in the excited-state intramolecular proton transfer also play important roles in the singlet oxygen quenching. Aloesaponarin I has a quenching rate constant larger than that of vitamin E and has a long duration of action due to its resistance to UV degradation and chemical attacks by singlet oxygen and free radicals.     

An improved method for basic hydrolysis of isoflavone malonylglucosides and quality evaluation of Chinese soy materials

Basic hydrolysis procedure is often included in the sample preparation in order to quantify malonylglucosides or acetylglucosides of soy materials. However, it is preferable not to use NaOH as a hydrolytic reagent considering the effect of its alkalinity on the successive injection to HPLC and low acidity of soy isoflavones. This paper presents an improved method for basic hydrolysis using ammonia as a hydrolytic reagent without the additional neutralization step. Moreover, by means of HPLC and LC-MS methods, a systematic quality evaluation of natural soy materials from Chinese markets were established and discussed, inclusive of soybeans, black soybeans, defatted soy flours, as well as the distribution of isoflavones in the seed coat, hypocotyl and cotyledon. The results indicate that HPLC profiling patterns of originating various isoflavone constituents of Chinese soybeans was similar to those of Japanese ones, and those of Chinese black soybeans was similar to those of American ones. The average content level of total soy isoflavones of Chinese soybeans and black soybeans were a little lower than that of American and Japanese ones. Additionally, the thorough analysis for Semen Sojae Praeparatum, a Chinese herbal medicine made from fermented black soybeans or soybeans was done for the first time and the characteristic of its HPLC profiling patterns shows the higher content of isoflavone glucosides and aglycones than those of natural soy materials.     

Artificial Peptide-Protein Necrosomes Promote Cell Death

The presence of disordered region or large interacting surface within proteins significantly challenges the development of targeted drugs, commonly known as the “undruggable” issue. Here, we report a heterogeneous peptide-protein assembling strategy to selectively phosphorylate proteins, thereby activating the necroptotic signaling pathway and promoting cell necroptosis. Inspired by the structures of natural necrosomes formed by receptor interacting protein kinases (RIPK) 1 and 3, the kinase-biomimetic peptides are rationally designed by incorporating natural or _D-amino acids, or connecting _D-amino acids in a retro-inverso (DRI) manner, leading to one RIPK3-biomimetic peptide PR3 and three RIPK1-biomimetic peptides. Individual peptides undergo self-assembly into nanofibrils, whereas mixing RIPK1-biomimetic peptides with PR3 accelerates and enhances assembly of PR3 . In particular, RIPK1-biomimetic peptide DRI-PR1 exhibits reliable binding affinity with protein RIPK3, resulting in specific cytotoxicity to colon cancer cells that overexpress RIPK3. Mechanistic studies reveal the increased phosphorylation of RIPK3 induced by RIPK1-biomimetic peptides, elucidating the activation of the necroptotic signaling pathway responsible for cell death without an obvious increase in secretion of inflammatory cytokines. Our findings highlight the potential of peptide-protein hybrid aggregation as a promising approach to address the “undruggable” issue and provide alternative strategies for overcoming cancer resistance in the future.