Study of 1-deoxy-1-(indol-3-yl)-L-sorbose, 1-deoxy-1-(indol-3-yl)-L-tagatose,and their analogs

Alkaline degradation of the ascorbigen 2-C-[(indol-3-yl)methyl]-alpha-L-xylo-hex-3-ulofuranosono-1,4-lactone (1a) led to a mixture of 1-deoxy-1-(indol-3-yl)-L-sorbose (2a) and 1-deoxy-1-(indol-3-yl)-L-tagatose (3a). The mixture of diastereomeric ketoses underwent acetylation and pyranose ring opening under the action of acetic anhydride in pyridine in the presence of 4-dimethylaminopyridine (DMAP) with the formation of a mixture of (E)-2,3,4,5,6-penta-O-acetyl-1-deoxy-1-(indol-3-yl)-L-xylo-hex-1-enitol (4a) and (E)-2,3,4,5,6-penta-O-acetyl-1-deoxy-1-(indol-3-yl)-L-lyxo-hex-1-enitol (5a), which were separated chromatographically. Deacetylation of 4a or 5a afforded cyclised tetrols, tosylation of which in admixture resulted in 1-deoxy-1-(indol-3-yl)-3,5-di-O-tosyl-alpha-L-sorbopyranose (12a) and 1-deoxy-1-(indol-3-yl)-4,5-di-O-tosyl-alpha-L-tagatopyranose (13a). Under alkaline conditions 13a readily formed 2-hydroxy-4-hydroxymethyl-3-(indol-3-yl)cyclopenten-2-one (15a) in 90% yield. Similar transformations were performed for N-methyl- and N-methoxyindole derivatives.     

Himalsamines A and B,two new amino sugar isomers from the leaves of Daphniphyllum himalaense subsp. macropodum

A phytochemical investigation performed on the leaves of Daphniphyllum himalaense has led to the characterization of two new amino sugars (1 and 2) and six known daphniphyllum alkaloids. The structures of new compounds were determined based on the interpretation of spectroscopic data. Some of the alkaloids were found to possess moderate to weak activity against the hepatitis C virus infection.     

Modification of optimal pH in l-arabinose isomerase from Geobacillus stearothermophilus for d-galactose isomerization

l-Arabinose isomerase from Geobacillus stearothermophilus (GSAI; EC 5.3.1.4) has been genetically evolved to increase the reaction rate toward d-galactose, which is not a natural substrate. To change the optimal pH of GSAI for d-galactose isomerization (pH optimum at 8.5), we investigated the single point mutations influencing the activity based on the sequences of the previously evolved enzymes. Among the seven point mutations found in the evolved enzymes, mutations at Val⁴⁰⁸ and Asn⁴⁷⁵ were determined to be highly influential mutation points for d-galactose isomerization activity. A random mutation was introduced into sites Val⁴⁰⁸ and Asn⁴⁷⁵ (X408V and X475N), and candidates were screened based on non-optimal pH conditions. Among the mutations of X408V and X475N, mutations of Q408V and R408V were selected. The optimal pH of the both mutations Q408V and R408V was shifted to pH 7.5. At the shifted optimal pH, the d-galactose isomerization activities of Q408V and R408V were 60 and 30% higher than that of the wild type at pH 8.5, respectively.     

Taenia crassiceps: absorption of hexoses and partial characterization of Na + -dependent glucose absorption by larvae

The uptake of ¹⁴C-fructose by T. crassiceps larvae was linear with respect to concentration. Uptake of 0.05 mM¹⁴C-fructose was not inhibited by 5.0 mM unlabeled fructose, tagatose, or sorbose. Fructose appears to enter larvae by diffusion only. The uptake of radioglucose and radiogalactose was not linear with respect to concentration at low substrate concentrations; at high substrate concentrations, the uptake of both hexoses was linear with respect to concentration. Inhibitor studies indicated that both glucose and galactose enter larvae by a combination of diffusion and a mediated process, and that these hexoses are mutually competitive inhibitors of one another. The uptake of glucose and galactose was also inhibited by α-and β-methyl glucoside, fucose, and phlorizin, but not by several amino acids, certain sugar analogs, nor ouabain. Glucose transport is Na⁺ sensitive; K⁺ was demonstrated to be a competitive inhibitor of Na⁺ activation of glucose uptake. After a 90-min incubation in 5 mM unlabeled glucose, larvae accumulated glucose against an apparent concentration difference. Although larvae appear freely permeable to ouabain, this compound had no apparent effect on glucose accumulation. The results of this study are compared with previous studies on Hymenolepis diminuta, Calliobothrium verticillatum, Hydatigera (Taenia) taeniaeformis, and mammalian systems.     

Tagatose: properties, applications, and biotechnological processes

d-Tagatose has attracted a great deal of attention in recent years due to its health benefits and similar properties to sucrose. d-Tagatose can be used as a low-calorie sweetener, as an intermediate for synthesis of other optically active compounds, and as an additive in detergent, cosmetic, and pharmaceutical formulation. Biotransformation of d-tagatose has been produced using several biocatalyst sources. Among the biocatalysts, l-arabinose isomerase has been mostly applied for d-tagatose production because of the industrial feasibility for the use of d-galactose as a substrate. In this article, the characterization of many l-arabinose isomerases and their d-tagatose production is compared. Protein engineering and immobilization of the enzyme for increasing the conversion rate of d-galactose to d-tagatose are also reviewed.     

Sustained release nitric oxide releasing nanoparticles: Characterization of a novel delivery platform based on nitrite containing hydrogel/glass composites

A new platform using biocompatible materials is presented for generating powders comprised of nanoparticles that release therapeutic levels of nitric oxide (NO) in a controlled and sustained manner. The capacity of these particles to retain and gradually release NO arises from their having combined features of both glassy matrices and hydrogels. This feature allows both for the generation of NO through the thermal reduction of added nitrite by glucose and for the retention of the generated NO within the dry particles. Exposure of these robust biocompatible nanoparticles to moisture initiates the sustained release of the trapped NO over extended time periods as determined both fluorimetrically and amperometrically. The slow sustained release is in contrast to the much faster release pattern associated with the hydration-initialed NO release in powders derived from glassy matrices. These glasses are prepared using trehalose and sucrose doped with either glucose or tagatose as the source of thermal electrons needed to convert nitrite to gNO. Significantly, the release profiles for the NO in the hydrogel/glass composite materials are found to be an easily tuned parameter that is modulated through the specific additives used in preparing the hydrogel/glass composites. The presented data raise the prospect that these new NO releasing nanoparticles can be easily formulated for use under a wide range of therapeutic circumstances.