The efficient synthesis of morphinandienone alkaloids by using a combination of hypervalent iodine(III) reagent and heteropoly acid

The non-phenolic coupling reaction of benzyltetrahydroisoquinolines (laudanosine derivatives) by using a hypervalent iodine(III) reagent is described. In general, chemical oxidation of laudanosine gives glaucine. In contrast to general chemical oxidizing reagent systems, the novel use of reagent combination of phenyliodine bis(trifluoroacetate) (PIFA), and heteropoly acid (HPA) afforded morphinandienone alkaloids in excellent yields. In order to achieve the coupling reaction with simple reaction procedure, the use of HPA supported on silica gel instead of HPA was demonstrated and sufficient yield was exerted again. The present reagent system, PIFA/HPA, was also applied to the oxidation of other non-phenolic benzyltetrahydroisoquinolines and the high yield conversion to morphinandienones was accomplished.     

Direct measurement of iron in serum by electrothermal atomic absorption spectrometry

A simple and rapid method is described for the determination of iron in serum by atomic absorption spectrometry with a graphite furnace atomiser. The serum is diluted 40 times with water, and injected into the graphite tube. Optimal conditions are established, and interferences from proteins and salts eliminated. Since the procedure requires no sample pretreatment such as protein precipitation or wet digestion, contamination and losses by co-precipitation are excluded. The method can determine any species of iron in serum.     

Reduced osteoblastic population and defective mineralization in osteopetrotic (op/op) mice

Osteopetrotic (op/op) mice fail to exhibit bone remodeling because of a defective osteoclast formation due to a lack of macrophage colony-stimulating factor. In this study, we investigated the femora of op/op mice to clarify whether the osteoblastic population and bone mineralization are involved in osteoclasts or their bone resorption. The op/op mice extended the meshwork of trabecular bones from the chondro-osseous junction to the diaphyseal region. In the femoral metaphyses of op/op mice, intense alkaline phosphatase (ALPase)-positive osteoblasts were observed on the metaphyseal bone in close proximity to the erosion zone of the growth plates. Von Kossa's staining revealed scattered mineralized nodules and a fine meshwork of mineralized bone matrices while the wild-type littermates developed well-mineralized trabeculae parallel to the longitudinal axis. In contrast to the metaphysis, some op/op diaphyses showed flattened osteoblasts with weak ALPase-positivity, and the other diaphyses displayed bone surfaces without a covering by osteoblasts. It is likely, therefore, that the osteoblastic population and activity were lessened in the op/op diaphyses. Despite the osteopetrotic model, von Kossa's staining demonstrated patchy unmineralized areas in the op/op diaphyses, indicating that a lower population and/or the activity of osteoblasts resulted in defective mineralization in the bone. Transmission electron microscopy disclosed few osteoblasts on the diaphyseal bones, and instead, bone marrow cells and vascular endothelial cells were often attached to the unmineralized bone. Osteocytes were embedded in the unmineralized bone matrix. Thus, osteoclasts appear to be involved in the osteoblastic population and activity as well as subsequent bone mineralization.     

A novel water-soluble Hantzsch 1,4-dihydropyridine compound that functions in biological processes through NADH regeneration

A novel Hantzsch 1,4-dihydropyridine derivative could function in an organic solvent-free solution, and thus it could function in biological systems. These functions can be accomplished through regeneration of the reduced form of nicotinamine adenine dinucleotide (NADH), an essential compound for living organisms. The results obtained here demonstrate the usefulness of a water-soluble Hantzsch 1,4-dihydropyridine derivative and its wide applicability as a chemical energy source, which drives various biological processes efficiently.     

The direct synthesis of thioesters using an intermolecular radical reaction of aldehydes with dipentafluorophenyl disulfide in water

The combination of the water-soluble radical initiator, 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (VA-044), and surfactant, cetyltrimethylammonium bromide (CTAB), was found to be the most suitable condition for the effective direct synthesis of useful active thioesters (pentafluorophenyl thioesters) in water.     

A Cyclized Helix‐Loop‐Helix Peptide as a Molecular Scaffold for the Design of Inhibitors of Intracellular Protein–Protein Interactions by Epitope and Arginine Grafting

The design of inhibitors of intracellular protein–protein interactions (PPIs) remains a challenge in chemical biology and drug discovery. We propose a cyclized helix‐loop‐helix (cHLH) peptide as a scaffold for generating cell‐permeable PPI inhibitors through bifunctional grafting: epitope grafting to provide binding activity, and arginine grafting to endow cell‐permeability. To inhibit p53–HDM2 interactions, the p53 epitope was grafted onto the C‐terminal helix and six Arg residues were grafted onto another helix. The designed peptide cHLHp53‐R showed high inhibitory activity for this interaction, and computational analysis suggested a binding mode for HDM2. Confocal microscopy of cells treated with fluorescently labeled cHLHp53‐R revealed cell membrane penetration and cytosolic localization. The peptide inhibited the growth of HCT116 and LnCap cancer cells. This strategy of bifunctional grafting onto a well‐structured peptide scaffold could facilitate the generation of inhibitors for intracellular PPIs.     

CONFIGURATIONS OF CAROTENOIDS IN THE REACTION CENTER and THE LIGHT-HARVESTING COMPLEX OF Rhodospirillum rubrum. NATURAL SELECTION OF CAROTENOID CONFIGURATIONS BY PIGMENT PROTEIN COMPLEXES

Abstract— Carotenoids extracted from the reaction center (RC), the light-harvesting complex (LH), and the chromatophore membrane of Rhodospirillum rubrum SI were analyzed by high-performance liquid chromatography. The chemical structures and the configurations of major components were determined by means of mass, Raman, electronic absorption and ¹H-NMR spectroscopy. The results indicated: (1) 15- cis -spirilloxanthin is bound to RC; (2) both all-frans-spirilloxanthin and aII-(ran.s-3,4-dihydrospirilloxanthin are bound to LH and (3) 13-cK-spirilloxanthin is additionally present in the chromatophore membrane. The natural selection of the carotenoid configurations, i.e. 15-ris by RC and aW-trans by LH, is discussed in relation to the physiological functions and the photophysical properties of isomeric carotenoids.     

Determination of total 3α-hydroxy bile acids in serum by a bioluminescent flow-injection system using a hollow-fibre reactor

A continuous-flow bioluminescence method for measuring total 3α-hydroxy bile acids in serum is described. A bacterial luciferase and NADH:FMN oxidoreductase are covalently co-immobilized on a CNBr-activated Sepharose 4B. A permeable membrane (hollow fibre) reactor is used for the introduction of NAD⁺ and bioluminescent reagent. The reagent permeates into the flow-stream due to the existing difference in ionic strength. The continuous-flow light-emitting system, in which the column filled with the immobilized bioluminescent enzyme is placed in front of a photomultiplier tube inside a photon counter, is versatile and simple. The technique was tested by comparing results with those obtained by fluorimetry. More than 20 samples an hour can be analyzed. Normal values for total bile acids content serum ranged from 1.0 to 7.5 μM, in agreement with those obtained by the other method. Excellent reproducibility, precision, and sensitivity are achieved.