Showing papers on "Pyranose published in 2011"

CHARMM additive all-atom force field for carbohydrate derivatives and its utility in polysaccharide and carbohydrate-protein modeling.

Abstract: Monosaccharide derivatives such as xylose, fucose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GlaNAc), glucuronic acid, iduronic acid, and N-acetylneuraminic acid (Neu5Ac) are important components of eukaryotic glycans. The present work details development of force-field parameters for these monosaccharides and their covalent connections to proteins via O-linkages to serine or threonine sidechains and via N-linkages to asparagine sidechains. The force field development protocol was designed to explicitly yield parameters that are compatible with the existing CHARMM additive force field for proteins, nucleic acids, lipids, carbohydrates, and small molecules. Therefore, when combined with previously developed parameters for pyranose and furanose monosaccharides, for glycosidic linkages between monosaccharides, and for proteins, the present set of parameters enables the molecular simulation of a wide variety of biologically-important molecules such as complex carbohydrates and glycoproteins. Parametrization included fitting to quantum mechanical (QM) geometries and conformational energies of model compounds, as well as to QM pair interaction energies and distances of model compounds with water. Parameters were validated in the context of crystals of relevant monosaccharides, as well NMR and/or x-ray crystallographic data on larger systems including oligomeric hyaluronan, sialyl Lewis X, O- and N-linked glycopeptides, and a lectin:sucrose complex. As the validated parameters are an extension of the CHARMM all-atom additive biomolecular force field, they further broaden the types of heterogeneous systems accessible with a consistently-developed force-field model.

A reoptimized GROMOS force field for hexopyranose‐based carbohydrates accounting for the relative free energies of ring conformers, anomers, epimers, hydroxymethyl rotamers, and glycosidic linkage conformers

Abstract: This article presents a reoptimization of the GROMOS 53A6 force field for hexopyranose-based carbohydrates (nearly equivalent to 45A4 for pure carbohydrate systems) into a new version 56A(CARBO) (nearly equivalent to 53A6 for non-carbohydrate systems). This reoptimization was found necessary to repair a number of shortcomings of the 53A6 (45A4) parameter set and to extend the scope of the force field to properties that had not been included previously into the parameterization procedure. The new 56A(CARBO) force field is characterized by: (i) the formulation of systematic build-up rules for the automatic generation of force-field topologies over a large class of compounds including (but not restricted to) unfunctionalized polyhexopyranoses with arbritrary connectivities; (ii) the systematic use of enhanced sampling methods for inclusion of experimental thermodynamic data concerning slow or unphysical processes into the parameterization procedure; and (iii) an extensive validation against available experimental data in solution and, to a limited extent, theoretical (quantum-mechanical) data in the gas phase. At present, the 56A(CARBO) force field is restricted to compounds of the elements C, O, and H presenting single bonds only, no oxygen functions other than alcohol, ether, hemiacetal, or acetal, and no cyclic segments other than six-membered rings (separated by at least one intermediate atom). After calibration, this force field is shown to reproduce well the relative free energies of ring conformers, anomers, epimers, hydroxymethyl rotamers, and glycosidic linkage conformers. As a result, the 56A(CARBO) force field should be suitable for: (i) the characterization of the dynamics of pyranose ring conformational transitions (in simulations on the microsecond timescale); (ii) the investigation of systems where alternative ring conformations become significantly populated; (iii) the investigation of anomerization or epimerization in terms of free-energy differences; and (iv) the design of simulation approaches accelerating the anomerization process along an unphysical pathway.

Sensing the anomeric effect in a solvent-free environment

Abstract: The anomeric effect is a chemical phenomenon that refers to an observed stabilization of six-membered carbohydrate rings when they contain an electronegative substituent at the C1 position of the ring. This stereoelectronic effect influences the three-dimensional shapes of many biological molecules. It can be manifested not only in this classical manner involving interaction of the endocyclic oxygen atom (O5) found in such sugars with the C1 substituent (endo-anomeric effect) but also through a corresponding interaction of the electronegative exocyclic substituent with O5 (exo-anomeric effect). However, the underlying physical origin(s) of this phenomenon is still not clear. Here we show, using a combination of laser spectroscopy and computational analysis, that a truncated peptide motif can engage the two anomers of an isolated sugar in the gas phase, an environment lacking extraneous factors which could confound the analysis. (Anomers are isomers that differ in the orientation of the substituent at C1.) Complexes formed between the peptide and the α- or β-anomers of d-galactose are nearly identical structurally; however, the strength of the polarization of their interactions with the peptide differs greatly. Natural bond order calculations support this observation, and together they reveal the dominance of the exo- over the endo-anomeric effect. As interactions between oxygen atoms at positions C1 and C2 (O1 and O2, respectively) on the pyranose ring can alter the exo/endo ratio of a carbohydrate, our results suggest that it will be important to re-evaluate the influence, and biological effects, of substituents at position C2 in sugars.

glmS Riboswitch binding to the glucosamine-6-phosphate α-anomer shifts the pKa toward neutrality.

Abstract: The glmS riboswitch regulates gene expression through a self-cleavage activity. The reaction is catalyzed with the assistance of the metabolite cofactor glucosamine-6-phosphate (GlcN6P), whose amino group is proposed to serve as the general acid during the reaction. This reaction is pH-dependent with a pKa that is lower than the observed pKa for the amine of GlcN6P in solution. GlcN6P, like other pyranose sugars, undergoes spontaneous and rapid interconversion between the α and β anomers at the C1 position. Here we demonstrate by NMR that the Bacillus anthracis glmS riboswitch selectively binds the α-anomer of GlcN6P with a maximum binding affinity of 0.36 mM and that binding is pH-dependent. We also report that the anomeric ratio between α and β is pH-dependent and the pKas of the two amines differ by 0.5 pH units, α being the higher of the two (pKa = 8.3). The pH dependence of binding reveals a pKa of 6.7, suggesting that the glmS RNA reduces the pKa of the GlcN6P amine by 1.6 units in the ground state....

Identification of a Catalytic Base for Sugar Oxidation in the Pyranose 2-Oxidase Reaction

Abstract: Pyranose 2-oxidase (P2O) catalyzes the oxidation of aldopyranoses to form 2-keto sugars and H(2)O(2) . In this study, the mechanistic role of the conserved residues His548 and Asn593 in P2O was investigated by using site-directed mutagenesis, transient kinetics, and pH-dependence studies. As single mutants of H548 resulted in mixed populations of noncovalently bound and covalently linked FAD, double mutants containing H167A were constructed, in which the covalent histidyl-FAD linkage was removed in addition to having the H548 mutation. Single mutants H548A, H548N, H548S, H548D and double mutants (with H167A) could not be reduced by D-glucose. For the H167A/H548R mutant, the flavin could be reduced by D-glucose with the reduction rate constant about 220 times lower than that of the H167A mutant. The pH-dependence studies of H167A/H548R indicated that the rate constant of flavin reduction increased about 360-fold upon a pH rise corresponding to pK(a) >10.1, whereas the reactions of the wild-type and H167A mutant enzymes were pH independent. Therefore, the data suggest that a pK(a) value of >10.1 in the mutant enzyme is associated with the Arg548 residue, and that this residue must be unprotonated to efficiently catalyze flavin reduction. The data imply that for the wild-type P2O, the conserved His548 should be unprotonated in the pH range studied. The unprotonated His548 can act as a general base to abstract the 2-hydroxyl proton of D-glucose and initiate hydride transfer from the substrate to the flavin. Studies of the single mutant N593H showed that the flavin reduction rate constant was 114 times lower than that of the wild-type enzyme and was pH independent, while the K(d) for D-glucose binding was 19 times greater.

Hydrogen bonding interactions between α-, β-glucose, and methacrylic acid

Abstract: Intermolecular interactions between α-, β-glucose, and methacrylic acid (MAA) have been investigated. Twenty-two possible conformations have been optimized at the DFT(B3LYP) level of theory with the 6-31G(d) basis set. The geometrical parameters for the most stable configurations of hydrogen bonding sites in the optimized systems have been determined. The binding energies ΔE bind have been calculated at the MP2/6-311++G(d,p) level of approximation taking into account the basis set superposition error (BSSE) and the zero-point vibrational energies corrections. Results indicate that the most stabilized complexes form hydrogen bonds either through carboxylic and hemiacetal oxygen atoms acting as proton acceptors. Both, α- and β-anomers are studied in the pyranose six-membered ring. In all complexes, the nuclear quadrupole coupling constants (χ) for 17O nuclei were obtained about 10.0 MHz, while for the 2H atoms they vary from ≈200.0 to ≈350.0 kHz.

Synthesis and properties of septanose carbohydrates

Abstract: Seven-atom ring sugars, called septanoses, are increasingly the focus of scientific inquiries because of their potential biological activities. This article details the synthesis, conformational analysis, and protein-binding properties of septanose carbohydrates. A distinction is drawn between septanoses that are substituted in the 6-position of the ring and those that are not. When a C-6 substituent is absent, the structure is essentially that of an aldohexose in its septanose, rather than furanose or pyranose, ring form; they may play as-of-yet unexplored roles in glycobiology. Septanoses having a hydroxymethyl group at C-6, on the other hand, are ring-expanded analogues of pyranoses. Syntheses have moved beyond the preparation of seven-membered ring monosaccharides to the development of septanosyl donors. These donors have been used in the synthesis of novel di- and trisaccharides that contain septanoses as well as a variety of glycoconjugates. Low-energy conformations adopted by septanoses have been organized based on ring substitution and stereochemistry. Instances where septanoses have been demonstrated to bind to natural proteins are presented and analyzed. The major conclusion drawn in the chapter is that advances in the synthesis of septanose carbohydrates now enable a detailed investigation of their activity in a number of biological contexts.

Computational and experimental investigations of mono-septanoside binding by Concanavalin A: correlation of ligand stereochemistry to enthalpies of binding

Abstract: Structure-energy relationships for a small group of pyranose and septanose mono-saccharide ligands are developed for binding to Concanavalin A (ConA). The affinity of ConA for methyl “manno” β-septanoside 7 was found to be higher than any of the previously reported mono-septanoside ligands. Isothermal titration calorimetry (ITC) in conjunction with docking simulations and quantum mechanics/molecular mechanics (QM/MM) modeling established the specific role of binding enthalpy in the structure–energy relations of ConA bound to natural mono-saccharides and unnatural mono-septanosides. An important aspect in the differential binding among ligands is the deformation energy required to reorganize internal hydroxyl groups upon binding of the ligand to ConA.

Synthesis of an Adenine Nucleoside Containing the (8′R) Epimeric Carbohydrate Core of Amipurimycin and Its Biological Study

Abstract: The (8′R) epimeric carbohydrate core 2 of amipurimycin was synthesized from d-glucose derived allylic alcohol 3 in 11 steps and 13% overall yield. The key steps involve an acid-catalyzed acetonide ring opening of 9 with concomitant formation of an unprecedented pyranose ring skeleton to give 2,7-dioxabicyclo[3.2.1]octane 10. The α-orientation of the furan ring in 10 readily allows the stereoselective β-glycosylation and opening of the furanose ring that on removal of protecting groups affords the pyranosyl adenine nucleoside 2. The antifungal and anticancer activities of 2 were studied.

Computational evidence for the substrate-assisted catalytic mechanism of O-GlcNAcase. A DFT investigation.

Abstract: A DFT computational investigation of the catalytic mechanism of O-GlcNAcase shows the existence of a substrate-assisted reaction pathway similar to that proposed in the literature on the basis of experimental evidence: the carbonyl oxygen of the N-acyl group bonded at C2 of the substrate pyranose ring attacks the anomeric carbon affording a bicyclic oxazoline intermediate and causing the breaking of the glycosidic bond and the expulsion of the aglycon. This occurs in a single kinetic step where the transfer of a proton from Asp-243 (behaving as a general base) to the leaving group is simultaneous to the cycle formation and departure of the aglycon (an activation barrier Ea of 16.5 kcal mol−1). Even if the other component of the catalytic dyad (Asp-242) is not actually involved in a proton transfer (as commonly suggested), it plays an important role in the catalysis through a complex network of hydrogen bonds that contribute to lower the activation barrier. The transition state of the process resembles an oxocarbenium ion (half chair conformation with an approximately planar sp2 anomeric carbon). Following the lines of previous experiments aimed to demonstrate the existence of a substrate-assisted mechanism, it is found that the computed Ea increases when the hydrogen atoms of the N-acetyl group are replaced with one, two and three F atoms and that a good linear correlation exists between the activation barrier Ea and the σ* Taft electronic parameter of the fluoro-substituted N-acetyl groups.

N-(2-aminobenzoyl)-N-methylhydrazones of aldehydes and aldoses and their cyclization to benzo-1,3,4-triazepine derivatives

Abstract: The products of the condensation of aliphatic aldehydes with N-(2-aminobenzoyl)-N-methylhydrazine exist in DMSO-d6 solution as tautomeric mixtures of linear aldohydrazone and cyclic benzo-1,3,4-triazepine forms. The linear tautomer predominates for 2-aminobenzoyl-N-methylhydrazones of aromatic aldehydes. A tautomeric equilibrium is observed in DMSO-d6 for the products of the condensation of the hydrazide of 2-aminobenzoic acid with a series of aldoses. This equilibrium exists between α,β-isomeric pyranose forms and the open aldosohydrazone form. Isomeric conversion to the seven-membered benzo-1,3,4-triazepine form is observed for the products of the condensation of aldoses with N-(2-aminobenzoyl)-N-methylhydrazine.

Rearrangement of 3-deoxy-D-erythro-hexos-2-ulose in aqueous solution: NMR evidence of intramolecular 1,2-hydrogen transfer.

Abstract: Selective (13)C- and (2)H-labeling, and (13)C NMR spectroscopy, have been used to show that the 1,2-dicarbonyl compound (osone), 3-deoxy-D-erythro-hexos-2-ulose (3-deoxy-D-glucosone) (1; 3DG), degrades to 3-deoxy-D-ribo-hexonic acid 2 and 3-deoxy-D-arabino-hexonic acid 3 exclusively via an intramolecular 1,2-hydrogen transfer mechanism in aqueous phosphate buffer at pH 7.5 at 37 °C. Acids 2 and 3 are produced in significantly different amounts (1:6 ratio) despite the prochiral C3 in 1, and two potential reaction mechanisms are considered to explain the observed stereoselectivity. One mechanism involves acyclic forms of 1 as reactants, whereas the other assumes cyclic pyranose reactants. In the former (2-keto-hydrate or 2KH mechanism), putative transition state structures based on density functional theory (DFT) calculations arise from the C1 hydrate form of acyclic 1 having the C1-H1 bond roughly orthogonal to the C2 carbonyl plane. The relative orientation of the alkoxide oxygen atom at C1 and the C2 carbonyl oxygen, and H-bonding between C(1)OH and the C2 carbonyl oxygen, contribute to the stability of the transition state. DFT calculations of the natural charges on individual atoms in the transition state show the migrating hydrogen to have an almost neutral charge, implying that it may more closely resemble a hydrogen atom than a hydride anion during transfer from C1 to C2. A second mechanism (2-keto-pyranose or 2KP mechanism) involving the cyclic 2-keto-pyranoses of 1 as reactants aligns the C1-H1 bond orthogonal to the C2 carbonyl plane in different ring conformations of both anomers, with the β-pyranose giving 3 and the α-pyranose giving 2. While both the 2KH and 2KP mechanisms are possible, the latter readily leads to a prediction of the reaction stereospecificity that is consistent with the experimental data.

Quantum mechanical interpretation of the IR Spectrum of 2-deoxy-D-ribose in the oh group stretching vibration region

Abstract: Within MP2/6-311++G(d,p)//DFT B3LYP/6-31 G(d,p) theory, taking into account the anharmonicity of the vibrations, we have calculated the vibrational spectra of all the conformers of the furanose, pyranose, and linear forms of the 2-deoxy-D-ribose molecule. Based on the calculation, we have interpreted the experimental IR spectrum of this molecule in the region of stretching vibrations of the OH groups. For the α and β anomers of the pyranose form of the molecule, we observe and explain the difference between the populations realized in the experiment and the calculated thermodynamic equilibrium values. We present the structures of the eight isomers of 2-deoxy-D-ribose determining its IR spectrum in a low-temperature inert matrix.

Ring cleavage reactions of methyl α-D-allopyranoside derivatives with phenylboron dichloride and triethylsilane.

Abstract: In the course of our studies on the regioselective carbon-oxygen bond cleavage of the benzylidene acetal group of hexopyranosides with a reducing agent, we found that a combination of a Lewis acid and a reducing agent triggered a ring-opening reaction of the pyranose ring of methyl α-D-allopyranosides The formation of an acyclic boronate ester by the attachment of a hydride ion at C-1 indicated that the unexpected endocyclic cleavage of the bond between the anomeric carbon atom and the pyranose ring oxygen atom proceeded via an oxacarbenium ion intermediate produced by the chelation between O5/O6 of the pyranoside and the Lewis acid, followed by nucleophile substitution with a hydride ion at C1

A chemoenzymatic synthesis of deoxy sugar esters involving stereoselective acetylation of hemiacetals catalyzed by CALB

Abstract: An extension of the scope of the chemoenzymatic strategy for the synthesis of stereochemically pure pyranose deoxy sugar esters of different carboxylic acids has been achieved. The objective of the work was to extend the strategy to the synthesis of furanose deoxy sugar derivatives and additionally, to N-Boc-protected amino acid esters. With all used carboxylic acids (deoxycholic acid, α-methoxyphenylacetic acid, N-Boc- l -phenylalanine and N-Boc- l -tyrosine) the lipase-catalyzed stereoselective acetylation of furanose or pyranose hemiacetal moiety as a key step afforded one desired stereochemically pure acetylated hemiacetal deoxy sugar ester in high de.

Synthesis Of Monomeric Forms Of α-Hydroxy-β-Methoxypropionaldehyde And 1:3-Dimethoxy-Propanone-2

Abstract: The compounds concerned in this communication are required for the synthesis of methylated hexoses which could not possess a pyranose structure. α-Hydroxy-β-methoxypropionaldehyde had not been obtained in the monomeric form, although the dimeride was prepared by Fisher and Bear1 and proved to be a crystalline substance melting at 120 to 121 C. which on heating with pyridine suffered rearrangement into the monomethyl ether of dihydroxyacetone. Alkaline condensation of this dimeride gave rise to sugars with branched chains.

Sugar derivative having a polymerizable group, and resist material using said sugar derivative

Abstract: Provided are pyranose derivatives and furanose derivatives, depicted in formulas (I) through (V), of glucose, mannose, psicose, sorbose, tagatose, allose, altrose, gulose, idose, or talose. (In the formulas, M1 represents a specific polymerizable group.)

Method of producing sugar fluorinated at anomeric position

Abstract: PROBLEM TO BE SOLVED: To provide an industrial method of producing sugar fluorinated at the anomeric position. SOLUTION: A hexose pyranosyl fluoride protector, a pentose pyranosyl fluoride protector, a hexose franosyl fluoride protector or a pentose franosyl fluoride protector can be produced by reacting a hexose pyranose protector, a pentose pyranose protector, a hexose franose protector or a pentose furanose protector respectively with sulfuryl fluoride (SO 2 F 2 ) in the presence of an organic alkali. The reaction may be carried out by further allowing the presence of [a salt or a complex comprised of an organic base and hydrogen fluoride] in the reaction system according to the need therefor. The industrial method of producing sugar fluorinated at the anomeric position can employ a low-cost fluorinating agent and a simple purification operation in its post-treatment process, has no restriction with respect to the material for constructing its reaction apparatus, and can be applied to a raw material substrate comprising a hydroxyl protected group at the 2-position that can be expected to exhibit the neighboring group participation. COPYRIGHT: (C)2011,JPO&INPIT