Stereoselective synthesis of β-N-glycosides through 2-deoxy-2-nitroglycal

An efficient, base-free protocol has been developed for the β-stereoselective synthesis of N-glycosides from 2-nitroglycal and secondary amines. Simple protection and deprotection manipulations on the N-glycosides pave a way for the synthesis of biologically significant1,2-diaminosugars and glycopeptides.     

Photosensitized Oxygenation of α-Pyran Derived from β-Ionone

Photosensitized oxygenation of α-pyran(l) (2,5,5,8a-tetramethyl-6,7,8,8a-tetrahydro-5H- l-benzopyran), in methanol using rose bengal, rapidly formed a stable peroxide (2).

The peroxide (2) gave 6,6-dimethyl-8-undecene-2,7,10-trione(11) at 140°C in xylene, and 8(or 9)-methoxy or hydroxy derivatives of 6,6-dimethyl-undecane-2,7,10-trione (12a or b) by hydrochloric acid.

These triketones (11 and 12a) were also obtained by a photo-reaction from the peroxide(2).     

Crystal structures of rare disaccharides, α-D-glucopyranosyl β-D-psicofuranoside, and α-D-galactopyranosyl β-D-psicofuranoside

The crystal structures of α-D-glucopyranosyl β-D-psicofuranoside and α-D-galactopyranosyl β-D-psicofuranoside were determined by a single-crystal X-ray diffraction analysis, refined to R(1)=0.0307 and 0.0438, respectively. Both disaccharides have a similar molecular structure, in which psicofuranose rings adopt an intermediate form between (4)E and (4)T(3). Unique molecular packing of the disaccharides was found in crystals, with the molecules forming a layered structure stacked along the y-axis.     

Soluble guanylate cyclase isoenzymes: The expression of α1, α2, β1, and β2 subunits in the benign and malignant breast tumors

Soluble guanylate cyclase (sGC) encompasses α and β subunits. This study examined the expression of α1, α2, β1, and β2 subunits in the malignant and benign breast tumors using the Western blot analysis. Both benign and malignant tumors showed a significantly higher expression of the α1 subunit in comparison with normal tissues (p < 0.0001). In contrast, the expression of α2 and β2 sGC were significantly lower in these tumors than normal tissues (p < .0015 and p < .001, p < .007 and p < .0001, respectively). The expression level of α1 sGC was significantly correlated with ER + PR+ (p < .0001). A significant correlation was also detected for sGC-α1 and -α2 expression with c-erbB2-negative status (p < .01). However, the expression level of sGC was not associated with tumor stage, tumor grade, or other clinicopathological features. In conclusion, as the expression of α1 sGC is upregulated and α2 and β2 sGC are downregulated in malignant breast tumors. Variations in the expression of sGC isoenzymes may be suggested as an indicator to confirm the enzyme antitumor activity.     

Hydrolysis of natural and synthetic substrates by α-l-fucosidase, β-d-glucuronidase and β-n-acetylhexosaminidase purified from molluscs

• 1.1. Several mollusc glycosidases have been studied for their activities towards natural substrates. α-l-Fucosidases from Chamelea gallina, Tapes rhomboideus and Mytilus edulis hydrolyze oligosaccharides (di, tri and pentasaccharides) with α1 → 2, α1 → 3 and α1 → 4 bonds, fucose-containing glycopeptides from bovine thyroglobulin and the porcine submandibular mucin (devoid of sialic acid); α-l-fucosidase from Littorina littorea hydrolyzes fucose-containing glycopeptides from bovine thyroglobulin.
• 2.2. β-d-Glucuronidase from L. littorea hydrolyzes hyaluronic acid, chondroitin 4-sulfate and heparin with a very low activity; however, it is much more active on oligosaccharides (from the above-mentioned macromolecules) containing non-reducing terminal glucuronyl residues.
• 3.3. β-N-Acetylhexosaminidase from Helicella ericetorum acts mainly with an endo-hydrolase activity on β1 → 4N-acetylhexosamine linkages of ovalbumin, ovomucoid, chitin, hyaluronic acid and chondroitin
• 4.4-sulfate; it has also a secondary exo-hydrolase activity on these substrates.

     

Molecular weights of wheat γ2-, β6-, α7-, α8- and α9-gliadins

The molecular weights of wheat γ₂-, β6-, α7-, α8- and α9-gliadins were calculated with the aid of a computer technique from sedimentation equilibrium data obtained in an ultracentrifuge equipped with photoelectric scanner. The dissociative solvents, all at pH 3.1 by addition of HCl, included 3 M urea, 0.15 M KCl; 8 M urea, 0.15 M KCl and 6 M guanidine-HCl. The minimum molecular weights for γ₂-, α7- and α9-gliadins, obtained in 6 M guanidine-HCl, were 34 600, 30 400 and 30 900, respectively. The β6- and α8-gliadins gave minimum molecular weights of 33 000 and 36 900, respectively, in 3 M urea, 0.15 M KCl.     

Inhibition- and acceptor-reaction studies of streptococcus mutans 6715 glucosyltransferases with 3-deoxysucrose, 3-deoxy-3-fluorosucrose,and α-dallopyranosyl β-d-fructofuranoside

Three new sucrose analogs modified at C-3 have been studied as inhibitors and substrates for the glucosyltransferases (glucansucrases) of Steptococcus mutans 6715. Although none of the analogs were found to be substrates for polymer synthesis with either the soluble-polysaccharide producing enzyme, GTF-S, or the insoluble-polysaccharide producing enzyme, GTF-I, 3-deoxysucrose and 3-deoxy-3-fluorosucrose were able to donate glycosyl residues for acceptor reactions with both enzymes. Modification at C-3 considerably decreased the binding at the active site of both enzymes, since all of the analogs had inhibition constants at least one order of magnitude greater than the K_m value for sucrose.     

Synthesis of 2-amino-2-deoxy- and 3-amino-3-deoxy-α-d-mannopyranosyl α-d-mannopyranoside by sequential osmylations of a dienic disaccharide

Partial oxyamination of 4,6-di-O-acetyl-2,3-dideoxy-α-d-erythro-hex-2-enopyranosyl 4,6-di-O-acetyl-2,3-dideoxy-α-d-erythro-hex-2-enopyranoside with chloramine-T and osmium tetraoxide gave 4,6-di-O-acetyl-2-deoxy-2-(p-toluene-sulfonamido)-α-d-mannopyranosyl 4,6-di-O-acetyl-2,3-dideoxy-α-d-erythro-hex-2-enopyranoside and its 3-deoxy-3-(p-toluenesulfonamido) regioisomer, each in 18–19% isolated yield. Osmium tetraoxide-catalyzed cis-hydroxylation of the remaining alkenic residue in these products led in high yields to the corresponding triols having the α-d-manno, α-d-manno configuration. These were N-desulfonylated (and simultaneously O-deacetylated) by the action of sodium in liquid ammonia to furnish 2-amino-2-deoxy-α-d-mannopyranosyl α-d-mannopyranoside and 3-amino-3-deoxy-α-d-mannopyranosyl α-d-mannopyranoside as new, trehalose-type amino sugars.     

Fuel-dependent,shape-selective,distinct blue and green photoluminescence from α-Bi2O3 and β-Bi2O3 synthesised using microwave combustion

In the current study, α-Bi₂O₃ and β-Bi₂O₃ were synthesised using a one-step, novel, solid–solid combustion technique. The reaction rate was increased with the use of microwaves (molecular heating) compared to direct or indirect heating. A strong relationship was observed between the fuel, polymorphic structure, shape and optical properties of the synthesised Bi₂O₃. Photoluminescence studies reveal that two major visible emissions are observed for all samples. The two emissions are distinct with a broad peak in blue and a narrow peak in green. The intensity of the green characteristic emission depends strongly on the heating method used for synthesis and is more intense for microwave-synthesised samples.     

Asymmetric acetalation of α,α-trehalose: Synthesis of α-d-galactopyranosyl α-d-glucopyranoside and 6-deoxy-6-fluoro-α-d-glucopyranosyl α-d-glucopyranoside

Selective acetalation of α,α-trehalose with ethyl or methyl isopropenyl ether and toluene-p-sulphonic acid in N,N-dimethylformamide gave the 4,6-isopropylidene acetal as the major product, isolated as its hexa-acetate 1 (38%). The gluco-galacto analogue 6 of α,α-trehalose was synthesized from 1 by the sequence: hydrolysis of the isopropylidene group with trifluoroacetic acid, mesylation of the resulting diol, benzoate displacement, and saponification of the product. Deacetylation of 1 followed by benzylation and hydrolysis of the acetal group furnished a hexa-O-benzyl derivative 9. Tosylation of the primary hydroxyl group in 9, treatment of the product with tetrabutylammonium fluoride in acetonitrile, and subsequent catalytic hydrogenolysis of the benzyl groups gave 6-deoxy-6-fluoro-α,α-trehalose (12). Compounds 6 and 12 and 6-deoxy-6-iodo-α,α-trehalose are substrates for cockchafer trehalase, but have very low V_max values.     

Catalytic versatility of trehalase: Synthesis of α-d-glucopyranosyl α-d-xylopyranoside from β-d-glucosyl fluoride and α-d-xylose

Trehalase was previously shown (see ref. 5) to hydrolyze α-d-glucosyl fluoride, forming β-d-glucose, and to synthesize α,α-trehalose from β-d-glucosyl fluoride plus α-d-glucose. Present observations further define the enzyme's separate cosubstrate requirements in utilizing these nonglycosidic substrates. α-d-Glucopyranose and α-d-xylopyranose were found to be uniquely effective in enabling Trichoderma reesei trehalase to catalyze reactions with β-d-glucosyl fluoride. As little as 0.2mm added α-d-glucose (0.4mm α-d-xylose) substantially increased the rate of enzymically catalyzed release of fluoride from 25mm β-d-glucosyl fluoride at 0°. Digest of β-d-glucosyl fluoride plus α-d-xylose yielded the α,α-trehalose analog, α-d-glucopyranosyl α-d-xylopyranoside, as a transient (i.e., subsequently hydrolyzed) transfer-product. The need for an aldopyranose acceptor having an axial 1-OH group when β-d-glucosyl fluoride is the donor, and for water when α-d-glucosyl fluoride is the substrate, indicates that the catalytic groups of trehalose have the flexibility to catalyze different stereochemical reactions.     

Geographie variation of α-amylase, β-amylase, β-glucanase,pullulanase and chitinase activity in germinating Hordeum spontaneum barley from Israel and Jordan

The enzyme activities of -amylase, -amylase, -glucanase, pullulanase and chitinase were determined in extracts of wild barley (Hordeum vulgare ssp. spontaneum) germinated for five days under axenic standard conditions. The material comprises 257 accessions, for 242 of which the botanical territory of origin in Israel or Jordan is known. The enzyme activities based on soluble protein in the extracts showed significant differences (P<0.001) among the eleven territories. The territorial moisture parameters mostly correlate with the enzyme activities. As determined by one gene or oligogenes, the significant territorial differences and the correlation with moisture are thought to reflect natural selection of genes responsible for favourable activity, or of genes linked to the enzyme coding loci, or in a coadaptive manner, of physiologically allied genes. Genes for high -glucanase activity at germination are probably coadaptive with genes for high -glucan content of the grain. The generally low starch content of wild barley grains probably makes any high -amylase activity unnecessary at the germination stage. An inverse relationship appears between -glucanase and chitinase activity; these two enzymes are also pathogenesis related proteins.     

Specificity of β1,4-galactosyltransferase inhibition by 2-naphthyl 2-butanamido-2-deoxy-1-thio-β-D-glucopyranoside

Inhibitors of Galactosyltransferase (GalT) have the potential of reducing the amounts of adhesive carbohydrates on secreted and cell surface-bound glycoproteins. We recently found a potent inhibitor of β4GalT, 2-naphthyl 2-butanamido-2-deoxy-1-thio-β-D-glucopyranoside (compound 612). In this work, we have tested compound 612 for the specificity of its inhibition and examined its effect on GalT, and on GlcNAc- and GalNAc-transferases in homogenates of different cell lines, as well as on recombinant glycosyltransferases. Compound 612 was found to be a specific inhibitor of β4GalT. The specificity of recombinant human β3GalT5 that also acts on GlcNAc-R substrates, revealed similarities to bovine milk β4GalT. However, 612 was a poor substrate and not an inhibitor for β3GalT5. To further determine the specific structures responsible for the inhibitory property of 612, we synthesized (2-naphthyl)-2-butanamido-2-deoxy-β-D-glucopyranosylamine (compound 629) containing nitrogen in the glycosidic linkage, and compared it to other naphthyl and quinolinyl derivatives of GlcNAc as substrates and inhibitors. Compound 629 was a substrate for both β4GalT and β3GalT5. This suggests that properties of 612 other than the presence of the naphthyl ring alone were responsible for its inhibitory action. The results suggest a usefulness of 612 in specifically blocking the synthesis of type 2 chains and thus epitopes attached to type 2 chains. In addition, 612 potently inhibits β4GalT in cell homogenates and thus allows assaying β3GalT activity in the presence of β4GalT.     

Force Generation via β-Cardiac Myosin,Titin, and α-Actinin Drives Cardiac Sarcomere Assembly from Cell-Matrix Adhesions

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Systemic Amyloidosis: Lessons from β2-Microglobulin

β₂-Microglobulin is responsible for systemic amyloidosis affecting patients undergoing long-term hemodialysis. Its genetic variant D76N causes a very rare form of familial systemic amyloidosis. These two types of amyloidoses differ significantly in terms of the tissue localization of deposits and for major pathological features. Considering how the amyloidogenesis of the β₂-microglobulin mechanism has been scrutinized in depth for the last three decades, the comparative analysis of molecular and pathological properties of wild type β₂-microglobulin and of the D76N variant offers a unique opportunity to critically reconsider the current understanding of the relation between the protein''s structural properties and its pathologic behavior.