Isolation and structural determination of a unique polysaccharide containing mannofuranose from the cell wall of the fungus <Emphasis Type="Italic">Acrospermum compressum</Emphasis>

The alkali-extractable and water-soluble fungal polysaccharide F1SS isolated from the cell wall of Acrospermum compressum has been studied by methylation analyses, reductive cleavage and 1D- and 2D-NMR spectroscopy. The polysaccharide consists of a regular disaccharide repeating unit with the structure: The mannan core was obtained by mild hydrolysis of the polysaccharide F1SS and its structure was deduced to be composed of a skeleton of α-(1→6)-mannopyranan, with around 1 out of 11 residues substituted at position 2 by short chains (one to six units) of 2-substituted mannopyranoses. DOSY experiments provided molecular sizes of 60 kDa and 2.5 kDa for the polysaccharide F1SS and the mannan core, respectively. This is the first report of a fungal mannofuranose-containing cell wall polysaccharide.     

Cell wall polysaccharides isolated from the fungus <Emphasis Type="Italic">Neotestudina rosatii</Emphasis>, one of the etiologic agents of mycetoma in man

The alkali-extractable water-soluble polysaccharides F1SS isolated from the cell wall of two isolates of the pathogen Neotestudina rosatii and one of Pseudophaeotrichum sudanense, which is now considered as a synonym of the former, have been studied by methylation analysis, GC–MS and NMR spectroscopy. The three polysaccharides differ mainly in their content in galactofuranose, and have the following idealized repeating unit:      

Concise synthesis of a heptasaccharide antigen found in the cell-wall lipopolysaccharide of Mycobacterium gordonae strain 990

A straight forward synthesis of a heptasaccharide part of the cell-wall lipopolysaccharide of Mycobacterium gordonae strain 990, known to have antigenicity, has been achieved in excellent yield. Judicious choice of protecting groups in the intermediates played a significant role throughout the synthesis. Most of the intermediate steps furnished satisfactory yield. Figure A concise synthesis of an antigenic heptasaccharide motif of the cell-wall glycolipid of Mycobacterium gordonae strain 990 in its preserved natural structure is presented using a general glycosylation condition and judicious protecting group manipulation C.D.R.I. communication number 7377.     

Concise synthesis of the pentasaccharide O-antigen of Escherichia coli O83:K24:H31 present in the Colinfant vaccine

A block synthetic approach is presented for the synthesis of the pentasaccharide repeating unit of the O-antigen of E. coli O83:K24:H31 strain, present in the “Colifant” vaccine. The target pentasaccharide has been synthesized by coupling a disaccharide with a trisaccharide in excellent yield. Yields are quite satisfactory in all intermediate steps. A concise synthesis of the pentasaccharide repeating unit of the O-antigen of E. coli O83:K24:H31 strain, present in the COLINFANT vaccine is presented. The target pentasaccharide has been synthesized following a block synthetic strategy by coupling a disaccharide with a trisaccharide in excellent yield.     

Expedient synthesis of the pentasaccharide repeating unit of the <Emphasis Type="Italic">O</Emphasis>-antigen of <Emphasis Type="Italic">Escherichia coli</Emphasis> O86 and its conformational analysis

Synthesis of the pentasaccharide with a 2-aminoethyl linker attached to the reducing end corresponding to the cell wall O-antigen of Escherichia coli O86 strain is reported. The synthetic strategy involves sequential glycosylation of suitably protected monosaccharide intermediates under similar glycosylation reaction conditions. Thioglycosides have been used as glycosyl donor throughout the synthetic strategy. Conformational analysis of the synthesized pentasaccharide has been carried out using 2D ROESY NMR spectral analysis and all atom explicit molecular dynamics (MD) simulation technique.

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Graphical abstract Facile synthesis of the pentasaccharide with a 2-aminoethyl linker attached to the reducing end corresponding to the cell wall O-antigen of Escherichia coli O86 strain is reported. Conformational analysis of the synthesized pentasaccharide has been carried out using 2D ROESY NMR spectral analysis and all atom explicit molecular dynamics (MD) simulation technique.

     

Click inspired synthesis of triazole-linked vanillin glycoconjugates

The 1,3-dipolar cycloaddition of deoxy-azido sugars 1 with alkyne derivatives of p-vanillin, 3-methoxy-4-(prop-2-ynyloxy)benzaldehyde (2) and 2-methoxy-1-(prop-2-ynyloxy)-4-((prop-2-ynyloxy)methyl)benzene) (4) to afford regioselective triazole-linked vanillinglycoconjugates 5 and 6 was investigated in the presence of CuI/DIPEA in dichloromethane. All the developed glycoconjugates were characterized on the basis of IR, NMR, and MS.

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Graphical abstract Triazolyl vanillin glycoconjugates via click chemistry

     

Aromaticity and electronic properties of Heterosuperbenzene (Heterohexabenzocoronene)

A global electrophilicity parameter and the aromaticity of some heterocyclic polyaromatic hydrocarbons were evaluated on the basis of DFT calculations. The substitution of carbon atoms by nitrogen atoms dramatically changes the global electrophilicity of the molecules, with the fully substituted molecule being the most electrophilic with a reactivity very close to that of fullerene. Figure Fully substituted heterohexabenzocoronene Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Molecular dynamics study of the initial stages of catalyzed single-wall carbon nanotubes growth: force field development

Effective force fields for Ni-C interactions developed by Yamaguchi and Maruyama for the formation of metallofullerenes are modified to simulate the catalyzed growth of single-wall carbon nanotubes on Ni_n clusters with n >20, and the reactive empirical bond order Brenner potential for C-C interactions is also revised to include the effect of the metal atoms on such interactions. Figure Force field parameters for carbon-metal interactions obtained from DFT calculations in small clusters.     

Selenylation modification: enhancement of the antioxidant activity of a <Emphasis Type="Italic">Glycyrrhiza uralensis</Emphasis> polysaccharide

Selenium (Se) is an essential trace element for human beings and many other forms of life. Organic selenium from natural foods has greater bioavailability and is safer than inorganic selenium species. In this article, the structural properties and antioxidant activities of a Glycyrrhiza uralensis polysaccharide (GUP) after selenylation modification were investigated. The GUP was extracted by water decoction and ethanol precipitation and purified via protein elimination using the trichloroacetic acid method and column chromatography. The purified product was subsequently modified by the nitric acid-sodium selenite (HNO₃-Na₂SeO₃) method. The selenized GUP (SeGUP) product was characterized by Fourier transform-infrared (FT-IR) spectroscopy, and its thermal stability, particle size, and antioxidant activities were investigated. FT-IR analysis indicated that the selenium in SeGUP existed mainly as O-Se-O. The thermal stability and particle size of SeGUP differed significantly from those of GUP. Moreover, compared to GUP, SeGUP exhibited greater antioxidant activities in vitro and in vivo. These results indicate that selenylation modification significantly enhances the antioxidant activity of SeGUP, increasing its potential for application as an antioxidant.

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Investigation of the intermolecular proton transfer in the supersystems adenine-methanol/ethanol/i-propanol: MP2 and DFT levels study

Twelve H-bonded supersystems constructed between the adenine tautomers and methanol, ethanol, and i-propanol were studied at the B3LYP and MP2 levels of theory using 6-311G(d,p) and 6-311++G(d,p) basis functions. The thermodynamic parameters of the complex formations were calculated in order to estimate the exact stability of the supersystems. It was proven that the calculated energy barriers of the alcohol-assisted proton transfers are about 60% lower than those of the intramolecular proton transfers in adenine found earlier (Gu and Leszczynski in J Phys Chem A 103:2744–2750, 1999). Figure H-bonded complex between i-propanol and adenine     

Quantitative trait loci identified for sugar related traits in a sugarcane (<Emphasis Type="Italic">Saccharum</Emphasis> spp.) cultivar × <Emphasis Type="Italic">Saccharum officinarum</Emphasis> population

The identification of markers linked to quantitative trait loci (QTLs) for increased sugar accumulation could improve the effectiveness of current breeding strategies in sugarcane. Progeny from a cross between a high sucrose producing cultivar, (denotes Australian plant breeding rights), and a Saccharum officinarum clone, IJ76-514 were grown in two field experiments in different years, and evaluated in the early and mid-season phases of crop maturity, to identify robust QTLs in affecting sucrose content in cane. Using an extensive genetic map constructed for with over 1,000 AFLP and SSR markers, a total of 37 QTLs were identified for brix and pol of which, 16 were detected in both experiments. Of these 37 QTL, 30 were clustered into 12 genomic regions in six of the eight homo(eo)logous groups. Each QTL explained from 3 to 9% of the phenotypic variation observed. Both positive and negative effects were identified and the location of the QTLs on linkage groups belonging to the same homo(eo)logy group suggested that a number of the QTLs were allelic forms of the same genes. Of the 37 QTLs identified, the majority were significant in both early and mature cane, but 8 were identified as early specific QTLs and 9 as mature cane QTLs. In total, 97 interactions were significant (P<10⁻⁵) and these were localised to 32 genomic regions of which 6 were detected with both years’ data. Models including all the QTLs explained from 37 to 66% of the total phenotypic variation, depending on the trait. The results will be subsequently applied in marker assisted breeding. denotes variety covered by Australian plant breeding rights.     

Quantification of sialic acids in red meat by UPLC-FLD using indoxylsialosides as internal standards

Herein we describe a UPLC-FLD-based method for the quantification of the sialic acid content of red meat, using a synthetic neuraminic acid derivative as an internal standard. X-Gal-α-2,6-N-propionylneuraminic acid was synthesized via a chemoenzymatic pathway and its hydrolytic stability was characterized. Known quantities of this compound were incubated with samples of red meat under sialic acid-releasing conditions. The released sialic acids were derivatized, analyzed by UPLC-FLD, and the Neu5Ac/Neu5Gc content of the meat sample was determined by comparison with the internal standard. A number of red meats were analyzed by this method with the following results (Neu5Ac μg/g tissue, Neu5Gc μg/g tissue ± s.d.): pork (68 ± 3, 15.2 ± 0.7), beef (69 ± 8, 36 ± 5), lamb (46 ± 2, 33 ± 1), rabbit (59 ± 2, 0.4 ± 0.4), and hare (50 ± 4, 1 ± 1). We envisage that this methodology will find application in investigating the health effects of dietary Neu5Gc.

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Proton transfer in some periodic molecular systems

The electronic structure of representative hydrogen bonded systems: hydrogen cyanide, imidazole and malonic acid have been studied at the non-empirical level. The role of the dimensionality on the potential barrier for the proton transfer has been examined. It was shown that it depends on the crystal structure and only in some cases like hydrogen cyanide or imidazole the relevant crystals may be considered as one-dimensional. However, for more complicated crystallographic structures, e.g. malonic acid, the evaluated barrier is strongly dependent on the dimensionality taken into account in our calculations. Figure Density of states for the imidazole dimer: MD-EQ- standard proton position (black line), MD-TR- proton position in the middle of the hydrogen bond (red line)     

3D-QSAR studies of Dipeptidyl peptidase IV inhibitors using a docking based alignment

Dipeptidyl peptidase IV (DPP-IV) deactivates the incretin hormones GLP-1 and GIP by cleaving the penultimate proline or alanine from the N-terminal (P1-position) of the peptide. Inhibition of this enzyme will prevent the degradation of the incretin hormones and maintain glucose homeostasis; this makes it an attractive target for the development of drugs for diabetes. This paper reports 3D-QSAR analysis of several DPP-IV inhibitors, which were aligned by the receptor-based technique. The conformation of the molecules in the active site was obtained through docking methods. The QSAR models were generated on two training sets composed of 74 and 25 molecules which included phenylalanine, thiazolidine, and fluorinated pyrrolidine analogs. The 3D-QSAR models are robust with statistically significant r², q², and values. The CoMFA and CoMSIA models were used to design some new inhibitors with several fold higher binding affinity. Figure The CoMFA contours around molecule D1T155 (a) steric contours - favored (green); disfavored (yellow) (b) electrostatic contours - electropositive (blue); electronegative (red)     

G2, G3, and complete basis set calculations of the thermodynamic properties of cis- and trans-triazene

Following our recent study on triazane, we present a follow-up study on the thermodynamic properties of triazane’s unsaturated analog, triazene. We predict optimized structural parameters, vibrational frequencies, enthalpies of formation, enthalpies of combustion, specific enthalpies of combustion, and proton affinities. Our results indicate that the cis form of triazene has a specific enthalpy of combustion of −15.2 kJ g⁻¹ and the trans form has a specific enthalpy of combustion of −14.7 kJ g⁻¹. Figure Structures of cis- and trans-triazane, N₃H₃     

G2, G3, and complete basis set calculations on the thermodynamic properties of triazane

As a follow-up study to our study on tetrazane (N₄H₆), we present computed thermodynamic properties of triazane (N₃H₅). Calculated properties include optimized geometries, infrared vibrations, enthalpy of formation, enthalpy of combustion, and proton affinities. We have also mapped the potential energy surface as the molecule is rotated about the N-N bond. We have predicted a specific enthalpy of combustion for triazane of about -20 kJ g⁻¹. Figure Schematic diagram of the dielectric barrier discharge (left) and typical temporal profiles of voltage and current, as obtained from the simulations (right)     

CoMFA study of distamycin analogs binding to the minor-groove of DNA: a unified model for broad-spectrum activity

A 3D-QSAR analysis has been carried out by comparative molecular field analysis (CoMFA) on a series of distamycin analogs that bind to the DNA of drug-resistant bacterial strains MRSA, PRSP and VSEF. The structures of the molecules were derived from the X-ray structure of distamycin bound to DNA and were aligned using the Database alignment method in Sybyl. Statistically significant CoMFA models for each activity were generated. The CoMFA contours throw light on the structure activity relationship (SAR) and help to identify novel features that can be incorporated into the distamycin framework to improve the activity. Common contours have been gleaned from the three models to construct a unified model that explains the steric and electrostatic requirements for antimicrobial activity against the three resistant strains. Figure A unified CoMFA model for broad-spectrum DNA minor-groove binders     

Docking studies on kinesin spindle protein inhibitors: an important cooperative ‘minor binding pocket’ which increases the binding affinity significantly

Fifteen KSP inhibitors were docked into the receptor and the binding mode was analyzed for the first time. It was considered that in addition to the main binding pocket all the inhibitors merged in, there exists a cooperative minor binding pocket, which could be explored for significantly increased binding affinity. In addition, a good linear relationship between the biological activities and the lowest binding free energies has also been found. This may help in predicting the binding affinity of newly designed KSP inhibitors. Figure Two binding pockets considered after the analysis. Seven docked ligands (compound 1–7) were overlapped at the binding site. All inhibitors tested interacted with the main pocket, while CK0106023, interacted also with the cooperative minor pocket mainly surrounded by Arg221 and Ala218. Coloring of the binding site surface are different ends of each amino acid residue: blue represents amino group while red means carboxyl     

Neighboring group stabilization by σ-holes

We have used density-functional theory to investigate the neighboring-group stabilization of iodine, arsenic, and phosphorus-centered oxyanion moieties in species such as deprotonated 2-iodoxybenzoic acid (IBX) and its analogs. The magnitudes of different stabilizing effects and further candidates for analogous stabilization are analyzed.