Sugar Amino Acid Research Articles

Amipurimycin: Total Synthesis of the Proposed Structures and Diastereoisomers.

The proposed diastereoisomers (1 a-d) together with their C8'-epimers (1 e-h) of amipurimycin, a unique antifungal peptidyl nucleoside antibiotic, have been synthesized for the first time. The synthetic approach is efficient and stereodivergent, and features a stereoselective aldol condensation to build the branched C9 sugar amino acid skeleton and a regio- and stereocontrolled gold(I)-catalyzed N-glycosylation to furnish the purine nucleoside. Analysis of the NMR data suggests that the previously assigned configuration of the tertiary C3' in amipurimycin should be of opposite configuration.

Amipurimycin: Total Synthesis of the Proposed Structures and Diastereoisomers

AbstractThe proposed diastereoisomers (1 a–d) together with their C8′‐epimers (1 e–h) of amipurimycin, a unique antifungal peptidyl nucleoside antibiotic, have been synthesized for the first time. The synthetic approach is efficient and stereodivergent, and features a stereoselective aldol condensation to build the branched C9 sugar amino acid skeleton and a regio‐ and stereocontrolled gold(I)‐catalyzed N‐glycosylation to furnish the purine nucleoside. Analysis of the NMR data suggests that the previously assigned configuration of the tertiary C3′ in amipurimycin should be of opposite configuration.

Crystal structure and hydrogen bonding in N-(1-de-oxy-β-d-fructo-pyranos-1-yl)-2-amino-isobutyric acid.

The title compound, alternatively called d-fructose-2-amino-isobutyric acid (FruAib), C10H19NO7, (I), crystallizes exclusively in the β-pyran-ose form, with two conformationally non-equivalent mol-ecules [(IA) and (IB)] in the asymmetric unit. In solution, FruAib establishes an equilibrium, with 75.6% of the population consisting of β-pyran-ose, 10.4% β-furan-ose, 10.1% α-furan-ose, 3.0% α-pyran-ose and <0.7% the acyclic forms. The carbohydrate ring in (I) has the normal 2C5 chair conformation and the amino acid portion is in the zwitterion form. Bond lengths and valence angles compare well with the average values from related pyran-ose structures. All carboxyl, hy-droxy and ammonium groups are involved in hydrogen bonding and form a three-dimensional network of infinite chains that are connected through homodromic rings and short chains. Intra-molecular hydrogen bonds bridge the amino acid and sugar portions in both mol-ecules. A comparative Hirshfeld surfaces analysis of FruAib and four other sugar-amino acids suggests an increasing role of intra-molecular heteroatom inter-actions in crystal structures with an increasing proportion of C-H bonds.

Sugar Loss Attributed to Non-Enzymatic Browning Corresponds to Reduce Calories Recovered in Low-Molecular-Weight Fraction

Health agencies state that total dietary energy intake should not exceed a maximal of 25% of calories derived from added sugars. Bakery products are major food sources that contribute to the added sugars intake; however potential sugars losses due to Maillard reaction and caramelization, occur at typical baking temperatures. In this study we employed markers associated with non-enzymatic browning, that corresponded to loss of free sugars, generation of α-dicarbonyl compounds with changes in caloric content of digestible constituents in sugar-amino acid model and cake formulations. Sugars losses in simple model systems that reached 100 percent after 40 min baking at baking temperatures of 150°C and 180°C corresponded to reduced calorie content, in fractions with a MW<3000 (p<0.05). In comparison, less gross energy calories from sucrose were lost after a similar heat treatment in sucrose-amino acid mixtures. Model cakes baked at 150°C and 180°C, respectively followed this trend with invert sugar, having greater losses losses (p<0.01) than cakes containing sucrose. We conclude that thermal temperatures typical of baking that result in non-enzymatic browning reactions, reduce both the total sugars and corresponding calories due to conversation to non-bioavailable high molecular weight browning products.

Self-Assembly of Fluorinated Sugar Amino Acid Derived α,γ-Cyclic Peptides into Transmembrane Anion Transport.

Syntheses of fluorinated sugar amino acid derived α,γ-cyclic tetra- and hexapeptides are reported. The IR, NMR, ESI-MS, CD, and molecular modeling studies of cyclic tetra- and hexapeptides showed C2 and C3 symmetric flat oval- and triangular-ring shaped β-strand conformations, respectively, which appear to self-assemble into nanotubes. The α,γ-cyclic hexapeptide (EC50 = 2.14 μM) is found to be a more efficient ion transporter than α,γ-cyclic tetrapeptide (EC50 = 14.75 μM). The anion selectivity and recognition of α,γ-cyclic hexapeptide with NO3- ion is investigated.

Anti-inflammatory effect of sugar-amino acid Maillard reaction products on intestinal inflammation model in vitro and in vivo

The Maillard reaction is a nonenzymatic reaction between an amino acid and a reducing sugar that usually occurs upon heating. This reaction occurs routinely in cooking, generates numerous products, which are collectively referred to as Maillard reaction products (MRPs) contributing to aroma and color features. Advanced glycation end-products (AGEs) transformed from MRPs are participated in many types of inflammation reaction. In this study, various sugar-amino acid MRPs were prepared from three different amino acids (lysine, arginine, and glycine) and sugars (glucose, fructose, and galactose) for 1 h with heating at 121 °C. Treatment of lipopolysaccharide-stimulated RAW264.7 macrophages with the MRPs decreased nitric oxide (NO) expression compared to control without MRPs treatment. MRPs derived from lysine and galactose (Lys-Gal MRPs) significantly inhibited NO expression. The retentate fraction of Lys-Gal MRPs with cut-off of molecular weight of 3–10 kDa (LGCM) suppressed NO expression more effectively than did Lys-Gal MRPs. The anti-inflammatory effect of LGCM was evaluated using a co-culture system consisting of Caco-2 (apical side) and RAW264.7 or THP-1 (basolateral side) cells to investigate the gut inflammation reaction by stimulated macrophage cells. In this system, LGCM prevented a decreased transepithelial electrical resistance, and decreased both tumor necrosis factor-α production in macrophages and interleukin (IL)-8 and IL-1β mRNA expression in Caco-2 cells. In co-culture and in vivo dextran sulfate sodium (DSS)-induced colitis model study, we also observed the anti-inflammatory activity of LGCM.

アンモニア酸化菌Nitrosomonas europaea ATCC 25978のグルタミン酸脱水素酵素活性に及ぼす糖-アミノ酸加熱反応生成物の影響

アンモニア酸化菌Nitrosomonas europaea ATCC 25978のグルタミン酸脱水素酵素活性に及ぼす糖-アミノ酸加熱反応生成物の影響

Acyclic αγα-Tripeptides with Fluorinated- and Nonfluorinated-Furanoid Sugar Framework: Importance of Fluoro Substituent in Reverse-Turn Induced Self-Assembly and Transmembrane Ion-Transport Activity.

Acyclic αγα-tripeptides derived from fluorinated-furanoid sugar amino acid frameworks act as reverse-turn inducers with a U-shaped conformation, whereas the corresponding nonfluorinated αγα-tripeptides show random peptide conformations. The NMR studies showed the presence of bifurcated weak intramolecular hydrogen bonding (F···HN) and N+···Fδ- charge-dipole attraction compel the amide carbonyl groups to orient antiperiplanar to the C-F bond, thus, demonstrating the role of the fluorine substituent in stabilizing the U-shaped conformation. The NOESY data indicate that the U-shaped tripeptides self-assembly formation is stabilized by the intermolecular hydrogen bonding between C═O···HN with antiparallel orientation. This fact is supported by ESI-MS data, which showed mass peaks up to the pentameric self-assembly, even in the gas phase. The morphological analysis by FE-SEM, on solid samples, showed arrangement of fibers into nanorods. The antiparallel self-assembled pore of the fluorinated tripeptides illustrates the selective ion-transport activity. The experimental findings were supported by DFT studies.

Predictable Conformational Diversity in Foldamers of Sugar Amino Acids

A systematic conformational search was carried out for monomers and homohexamers of furanoid β-amino acids: cis-(S,R) and trans-(S,S) stereoisomers of aminocyclopentane carboxylic acid (ACPC), two different aminofuranuronic acids (AFUα and AFUβ), their isopropylidene derivatives (AFU(ip)), and the key intermediate β-aminotetrahydrofurancarboxylic acid (ATFC). The stereochemistry of the building blocks was chosen to match that of the natural sugar amino acid (xylose and ribose) precursors (XylAFU and RibAFU). The results show that hexamers of cis-furanoid β-amino acids show great variability: while hydrophobic cyclopentane (cis-ACPC)6 and hydrophilic (XylAFUα/β)6 foldamers favor two different zigzagged conformation as hexamers, the backbone fold turns into a helix in the case of (cis-ATFC)6 (10-helix) and (XylAFU(ip))6 (14-helix). Trans stereochemistry resulted in hexamers exclusively with the right-handed helix conformation, (H12P)6, regardless of their polarity. We found that the preferred oligomeric structure of XylAFUα/β is conformationally compatible with β-pleated sheets, while that of the trans/(S,S) units matches with α-helices of proteins.

Synthesis, SAR and biological studies of sugar amino acid-based almiramide analogues: N-methylation leads the way.

Leishmaniasis, caused by the protozoan parasites of the genus Leishmania, is one of the most neglected diseases endemic in many continents posing enormous global health threats and therefore the discovery of new antileishmanial compounds is of utmost urgency. The antileishmanial activities of a library of sugar amino acid-based linear lipopeptide analogues were examined with the aim to identify potential drug candidates to treat visceral leishmaniasis. It was found that among the synthesized analogues, most of the permethylated compounds exhibited more activity in in vitro studies against intra-macrophagic amastigotes than the non-methylated analogues. SAR and NMR studies revealed that introduction of the N-methyl groups inhibited the formation of any turn structure in these molecules, which led to their improved activities.

NaCl-CaCl2 treatment enhancing nutritional and functional quality of mung bean sprouts

In this study, the effects of NaCl, CaCl2 and NaCl-CaCl2 treatments on the growth profiles, nutritional quality, phytic acid degradation-lower inositol phosphate formation system of germinated mung bean were investigated. Mung bean seeds were germinated at 30 oC in darkness for 4 days and sprayed solutions containing distilled water, 1.6 mM NaCl, 6 mM CaCl2, and 1.6 mM NaCl plus 6 mM CaCl2 every 1 h . Samples were collected every 2 days in liquid nitrogen for experiments and each experiment was repeated three times. The results showed that the NaCl-CaCl2 treatment improved nutritional quality significantly for the higher content of ascorbic acid, soluble sugar and free amino acid content in mung bean sprouts. Meanwhile, NaCl-CaCl2 treatment was also the most effective way to improve the degradation of phytic acid by enhancing phytase activity and the related gene expressions. This led to a higher level of the lower inositol phosphate content in mung bean sprouts. These results suggest that NaCl-CaCl2 treatment had a better influence on improving nutritional and functional quality of mung bean sprouts than NaCl and CaCl2.

C-3 epimers of sugar amino acids as foldameric building blocks: improved synthesis, useful derivatives, coupling strategies.

To obtain key sugar derivatives for making homooligomeric foldamers or α/β-chimera peptides, economic and multigram scale synthetic methods were to be developed. Though described in the literature, the cost-effective making of both 3-amino-3-deoxy-ribofuranuronic acid (H-t X-OH) and its C-3 epimeric stereoisomer, the 3-amino-3-deoxy-xylofuranuronic acid (H-c X-OH) from D-glucose is described here. The present synthetic route elaborated is (1) appropriate for large-scale synthesis; (2) reagent costs reduced (e.g. by a factor of 400); (3) yields optimized are ~80% or higher for all six consecutive steps concluding -t X- or -c X- and (4) reaction times shortened. Thus, a new synthetic route step-by-step optimized for yield, cost, time and purification is given both for D-xylo and D-ribo-amino-furanuronic acids using sustainable chemistry (e.g. less chromatography with organic solvents; using continuous-flow reactor). Our study encompasses necessary building blocks (e.g. -X-OMe, -X-OiPr, -X-NHMe, Fmoc-X-OH) and key coupling reactions making -Aaa-t X-Aaa- or -Aaa-t X-t X-Aaa- type "inserts". Completed for both stereoisomers of X, including the newly synthesized Fmoc-c X-OH, producing longer oligomers for drug design and discovery is more of a reality than a wish.

Structural Features for Furan-Derived Fruity and Meaty Aroma Impressions

Furan derivatives are part of nearly all food aromas. They are mainly formed by thermal degradation of carbohydrates and ascorbic acid and from sugar-amino acid interactions during food processing. Caramel-like, sweet, fruity, nutty, meaty, and burnt odor impressions are associated with this class of compounds. In the presented work, structure-activity relationship (SAR) investigations are performed on a series of furan derivatives in order to find structural subunits, which are responsible for the particular characteristic flavors. Therefore, artificial neural networks are applied on a set of 35 furans with the aroma categories "meaty" or "fruity" to calculate a classification rule and class boundaries for these two aroma impressions. By training a multilayer perceptron network architecture with a backpropagation algorithm, a correct classification rate of 100% is obtained. The neural network is able to distinguish between the two studied groups by using the following significant descriptors as inputs: number of sulfur atoms, Looping Centric Information Index, Folding Degree Index and Petitjean Shape Indices. Finally, the results clearly demonstrate that artificial neural networks are successful tools to investigate non-linear qualitative structure-odor relationships of aroma compounds.

Diastereoselective synthesis of furanose and pyranose substituted glycine and alanine derivatives via proline-catalyzed asymmetric α-amination of aldehydes

A concise organocatalytic route toward the synthesis of furanose and pyranose substituted glycine and alanine derivatives is reported. These compounds are core structural units of some of the naturally available antibiotics and antifungal agents. Proline-catalyzed asymmetric α-amination of aldehydes derived from sugars is used as the key reaction to synthesize twelve sugar amino acid derivatives. The asymmetric transformations proceeded in good yields and with good to excellent diastereoselectivity. The application of the synthesized amino acids is demonstrated by synthesizing a tripeptide containing one of them.

Influence of Linker Length on Conformational Preferences of Glycosylated Sugar Amino Acid Foldamers.

Glycosylation of foldamers derived from furanoid sugar amino acids with mannose and a propyltriazole linker results in an unprecedented 16/10 mixed-turn structure in the glycopeptides in water, with a preference for the higher-order structure irrespective of the stereochemistry of the starting foldamer. This is in stark contrast to the structures displayed by the same oligomers in water when mannosylated with a two-carbon-shorter methyltriazole linker: 16-membered turn structure in the cis-foldamer and 10-membered in its trans congener. This demonstrates the defining influence of the linker length on the structural preference of these novel glycopeptide mimics.

Conformational studies of glycosylated cyclic oligomers of furanoid sugar amino acids

Glycosylation of molecules improve their pharmacological and pharmacokinetic properties. In the current manuscript, we have explored the effect of glycosylation on the structure and function of conformationally well-defined small ring homooligomers derived from a structurally diverse library of sugar amino acids (SAA). Conformational analyses carried out by NMR suggested that these cyclic dimers and trimers have well-defined structures in solution. MD simulations performed based on the restraints obtained from NMR revealed that C2H and CO are positioned outside the plane of the ring and NHs are pointed inside the ring. It was encouraging to note that while the cyclic non-glycosylated homooligomers did not show any antimicrobial activity at all, their glycosylated counterparts showed relatively better activity. The modular design developed here is amenable to further improvement and can serve as a tool to investigate many molecular recognition processes.

Origin of problems related to Staudinger reduction in carbopeptoid syntheses.

We report the solid phase synthesis of -GG-X-GG- type α/β-carbopeptoids incorporating RibAFU(ip) (1a, tX) or XylAFU(ip) (2a, cX) sugar amino acids. Though coupling efficacy is moderate, both the lengthier synthetic route using Fmoc derivative (e.g., Fmoc-RibAFU(ip)-OH) and the azido derivative (e.g., N3-RibAFU(ip)-OH) via Staudinger reaction with nBu3P can be successfully applied. Both X-ray diffraction, 1H- and 31P-NMR, and theoretical (QM) data support and explain why the application of Ph3P as Staudinger reagent is "ineffective" in the case of a cis stereoisomer, if cX is attached to the preceding residue with a peptide (-CONH-) bond. The failure of the polypeptide chain elongation with N3-cX originates from the "coincidence" of a steric crowdedness and an electronic effect disabling the mandatory nucleophilic attack during the hydrolysis of a quasi penta-coordinated triphenylphosphinimine. Nevertheless, the synthesis of the above α/β-chimera peptides as completed now by a new pathway via 1,2-O-isopropylidene-3-azido-3-deoxy-ribo- and -xylo-furanuronic acid (H-RibAFU(ip)-OH 1a and H-XylAFU(ip)-OH 2a) coupled with N-protected α-amino acids on solid phase could serve as useful examples and starting points of further synthetic efforts.

ChemInform Abstract: Benzylidene Acetal Protecting Group as Carboxylic Acid Surrogate: Synthesis of Functionalized Uronic Acids and Sugar Amino Acids.

Direct oxidation of the 4,6-O-benzylidene acetal protecting group to C-6 carboxylic acid has been developed that provides an easy access to a wide range of biologically important and synthetically challenging uronic acid and sugar amino acid derivatives in good yields. The RuCl3 -NaIO4 -mediated oxidative cleavage method eliminates protection and deprotection steps and the reaction takes place under mild conditions. The dual role of the benzylidene acetal, as a protecting group and source of carboxylic acid, was exploited in the efficient synthesis of six-carbon sialic acid analogues and disaccharides bearing uronic acids, including glycosaminoglycan analogues.

Disease Severity Index as It Affects Responses in Potato Virus X–Challenged Potato Varieties

ABSTRACTPotato (Solanum tuberosum L.) is an important vegetable crop but can have significant yield loss due to disease, including those caused by viruses. The physiology of host plants can be affected by viruses, which can lead to symptom expression. Study of biochemical activities helps to understand the phenomena of plant disease resistance and can be useful in screening for natural resistance in host plants against viruses. Biochemical activities were analyzed among varieties from potato rated as being in susceptible (S), moderately susceptible (MS), and moderately resistant (MR) reaction groups on the basis of disease severity index. Reaction group status was confirmed through enzyme-linked immunosorbent assay (ELISA) of potato germplasm showing symptoms of potato virus X (PVX). Phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO), and sugar, soluble protein, and total amino acids contents were compared in virus-infected potato varieties from the reaction groups. There was not much variation in PAL activity among varieties in the same reaction group. The PPO and total sugar contents were lower in varieties of the MR reaction group compared to S varieties. Total soluble protein content was higher in S and MS varieties. Amino acid content was low in S and MS reaction groups. Comparison of biochemical analysis in varieties based on reaction groups against PVX could be helpful in selection of varieties for better yield.

Horst Kessler

Horst Kessler