Maltose Derivatives Research Articles

Sporangimicins A-D, acylated maltose derivatives from a rare actinomycete of the genus Pseudosporangium.

Sporangimicins A-D (1-4), four anomeric pairs of diacyl disaccharides that represent a new metabolite class, were discovered from the culture extract of an actinomycete Pseudosporangium sp. RD061809. Compounds 1-4 caused peak separation in the HPLC chromatogram and partial duplication of the NMR resonances by anomeric interconversion of a maltose core modified at the two sugar 6-positions with an isobutanoyl and a methyl-branched long-chain dienoyl groups. A highlight of the structure elucidation was application of Ohrui-Akasaka's method to a chromatographically inseparable mixture of 3 and 4, which proved the composition ratio of 3 and 4 to be 82:18 and the R/S ratio at the anteiso-methyl bearing chiral center in 3 to be 66:34. Compounds 1-4 showed antimicrobial activity against Gram-positive bacteria and modest cytotoxicity toward P388 murine leukemia cells.

Synthesis of a Series of Trimeric Branched Glycoconjugates and Their Applications for Supramolecular Gels and Catalysis.

Carbohydrate-derived molecular gelators have found many practical applications as soft materials. To better understand the structure and molecular gelation relationship and further explore the applications of sugar-based gelators, we designed and synthesized eight trimeric branched sugar triazole derivatives and studied their self-assembling properties. These included glucose, glucosamine, galactose, and maltose derivatives. Interestingly, the gelation properties of these compounds exhibited correlations with the peripheral sugar structures. The maltose derivative did not form gels in the tested solvents, but all other compounds exhibited gelation properties in at least one of the solvents. Glucose derivatives showed superior performance, followed by glucosamine derivatives. They typically formed gels in toluene and alcohols; some formed gels in ethanol-water mixtures or DMSO water mixtures. The glycoclusters 9 and 10 demonstrated rate acceleration for the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. These were further studied for their metallogels formation properties, and the copper metallogels from compound 9 were successfully utilized to catalyze click reactions. These metallogels were able to form a gel column, which was effective in converting the reactants into the triazole products in multiple cycles. Moreover, the same gel column was used to transform a second click reaction using different reactants. The synthesis and characterization of these compounds and their applications for catalytic reactions were discussed.

Metabolic Responses to Arsenite Exposure Regulated through Histidine Kinases PhoR and AioS in Agrobacterium tumefaciens 5A.

Arsenite (AsIII) oxidation is a microbially-catalyzed transformation that directly impacts arsenic toxicity, bioaccumulation, and bioavailability in environmental systems. The genes for AsIII oxidation (aio) encode a periplasmic AsIII sensor AioX, transmembrane histidine kinase AioS, and cognate regulatory partner AioR, which control expression of the AsIII oxidase AioBA. The aio genes are under ultimate control of the phosphate stress response via histidine kinase PhoR. To better understand the cell-wide impacts exerted by these key histidine kinases, we employed 1H nuclear magnetic resonance (1H NMR) and liquid chromatography-coupled mass spectrometry (LC-MS) metabolomics to characterize the metabolic profiles of ΔphoR and ΔaioS mutants of Agrobacterium tumefaciens 5A during AsIII oxidation. The data reveals a smaller group of metabolites impacted by the ΔaioS mutation, including hypoxanthine and various maltose derivatives, while a larger impact is observed for the ΔphoR mutation, influencing betaine, glutamate, and different sugars. The metabolomics data were integrated with previously published transcriptomics analyses to detail pathways perturbed during AsIII oxidation and those modulated by PhoR and/or AioS. The results highlight considerable disruptions in central carbon metabolism in the ΔphoR mutant. These data provide a detailed map of the metabolic impacts of AsIII, PhoR, and/or AioS, and inform current paradigms concerning arsenic–microbe interactions and nutrient cycling in contaminated environments.

Nonplanar Macrocycle Consisting of Four Pyridine and Phenol Units Connected with Acetylene Bonds Displaying Preferential Binding to Maltoside over Monosaccharides.

A nonplanar macrocycle consisting of four pyridine-acetylene-phenol units was developed as a host for saccharide guest molecules. The macrocycle was found to strongly associate with a lipophilic maltose derivative, with an association constant of 107 M-1, over monosaccharide derivatives, for which much smaller association constants were determined, ranging from 103 M-1 to 104 M-1. The macrocycle was found to adopt a boat-like conformation, encapsulating β-d-maltoside in a twisted manner through approximately seven intermolecular hydrogen bonds.

Characterization of Protonated Model Disaccharides from Tandem Mass Spectrometry and Chemical Dynamics Simulations.

The fragmentation mechanisms of prototypical disaccharides have been studied herein by coupling tandem mass spectrometry (MS) with collisional chemical dynamics simulations. These calculations were performed by explicitly considering the collisions between the protonated sugar and the neutral target gas, which led to an ensemble of trajectories for each system, from which it was possible to obtain reaction products and mechanisms without pre-imposing them. The β-aminoethyl and aminopropyl derivatives of cellobiose, maltose, and gentiobiose were studied to observe differences in both the stereochemistry and the location of the glycosidic linkage. Chemical dynamics simulations of MS/MS and MS/MS/MS were used to suggest some primary and secondary fragmentation mechanisms for some experimentally observed product ions. These simulations provided some new insights into the fundamentals of the unimolecular dissociation of protonated sugars under collisional induced dissociation conditions.

Synthesis of [¹⁸F]-labelled maltose derivatives as PET tracers for imaging bacterial infection.

To develop novel positron emission tomography (PET) agents for visualization and therapy monitoring of bacterial infections. It is known that maltose and maltodextrins are energy sources for bacteria. Hence, (18)F-labelled maltose derivatives could be a valuable tool for imaging bacterial infections. We have developed methods to synthesize 4-O-(α-D-glucopyranosyl)-6-deoxy-6-[(18)F]fluoro-D-glucopyranoside (6-[(18)F]fluoromaltose) and 4-O-(α-D-glucopyranosyl)-1-deoxy-1-[(18)F]fluoro-D-glucopyranoside (1-[(18)F]fluoromaltose) as bacterial infection PET imaging agents. 6-[(18)F]fluoromaltose was prepared from precursor 1,2,3-tri-O-acetyl-4-O-(2',3',-di-O-acetyl-4',6'-benzylidene-α-D-glucopyranosyl)-6-deoxy-6-nosyl-D-glucopranoside (5). The synthesis involved the radio-fluorination of 5 followed by acidic and basic hydrolysis to give 6-[(18)F]fluoromaltose. In an analogous procedure, 1-[(18)F]fluoromaltose was synthesized from 2,3, 6-tri-O-acetyl-4-O-(2',3',4',6-tetra-O-acetyl-α-D-glucopyranosyl)-1-deoxy-1-O-triflyl-D-glucopranoside (9). Stability of 6-[(18)F]fluoromaltose in phosphate-buffered saline (PBS) and human and mouse serum at 37 °C was determined. Escherichia coli uptake of 6-[(18)F]fluoromaltose was examined. A reliable synthesis of 1- and 6-[(18)F]fluoromaltose has been accomplished with 4-6 and 5-8% radiochemical yields, respectively (decay-corrected with 95 % radiochemical purity). 6-[(18)F]fluoromaltose was sufficiently stable over the time span needed for PET studies (∼96% intact compound after 1-h and ∼65% after 2-h incubation in serum). Bacterial uptake experiments indicated that E. coli transports 6-[(18)F]fluoromaltose. Competition assays showed that the uptake of 6-[(18)F]fluoromaltose was completely blocked by co-incubation with 1 mM of the natural substrate maltose. We have successfully synthesized 1- and 6-[(18)F]fluoromaltose via direct fluorination of appropriate protected maltose precursors. Bacterial uptake experiments in E. coli and stability studies suggest a possible application of 6-[(18)F]fluoromaltose as a new PET imaging agent for visualization and monitoring of bacterial infections.

Specific maltose derivatives modulate the swarming motility of nonswarming mutant and inhibit bacterial adhesion and biofilm formation by Pseudomonas aeruginosa.

We have demonstrated that specific synthetic maltose derivatives activate the swarming motility of a Pseudomonas aeruginosa nonswarming mutant (rhlA) at low concentration, but inhibit it at high concentration. Although these molecules are not microbicidal, active maltose derivatives with bulky hydrocarbon groups inhibited bacterial adhesion, and exhibited biofilm inhibition and dispersion (IC50 ~20 μM and DC50 ~30 μM, respectively). Because the swarming motility of the rhlA mutant is abolished by the lack natural rhamnolipids, the swarming activation suggests that maltose derivatives are analogues of rhamnolipids. Together, these results suggest a new approach of controlling multiple bacterial activities (bacterial adhesion, biofilm formation, and swarming motility) by a set of disaccharide-based molecules.

Effect of distal sugars and interglycosidic linkage on the N-glycoprotein linkage region conformation: synthesis and X-Ray crystallographic investigation of β-1-N-alkanamide derivatives of cellobiose and maltose as disaccharide analogs of the conserved chitobiosylasparagine linkage

The linkage region constituents, 2-deoxy-2-acetamido-β-D-glucopyranose (GlcNAc) and L-asparagine (Asn) are conserved in the N-glycoproteins of all eukaryotes. Elucidation of the structure and conformation of the linkage region of glycoproteins is important to understand the presentation and dynamics of the carbohydrate chain at the protein/cell surface. Earlier crystallographic studies using monosaccharide models and analogs of N-glycoprotein linkage region have shown that the N-glycosidic torsion, ϕN, is more influenced by the structural variation in the sugar part than that of the aglycon moiety. To access the influence of distal sugar as well as interglycosidic linkage (α or β) on the N-glycosidic torsion angles, cellobiosyl and maltosyl alkanamides have been synthesized and structural features of seven of these analogs have been characterized by X-ray crystallography. Comparative analysis of the seven disaccharide analogs with the reported monosaccharide analogs showed that the ϕN value of cellobiosyl analogs deviate ~9° with respect to GlcβNHAc. In the case of maltosyl analogs, deviation is more than 18°. These deviations indicate that the N-glycosidic torsion is influenced by addition of distal sugar as well as with respect to inter glycosidic linkage (α or β); it is less influenced by changes occurring at the aglycon. The χ₂ value of alkanamide derived from glucose, cellobiose and maltose exhibit a large range of variations (from 1.6° to -109.9°). This large span of χ₂ value suggests the greater degree of rotational freedom around C1'-C2' bond which is restricted in GlcNAc alkanamides. The present finding explicitly proved the importance of molecular architecture in the N-glycoproteins linkage region to maintain the linearity, planarity and rigidity. These factors are necessary for N-glycan to serve role in inter- as well as intramolecular carbohydrate-protein interactions.

Identification of Bacillus selenitireducens MLS10 maltose phosphorylase possessing synthetic ability for branched α-d-glucosyl trisaccharides

We discovered an inverting maltose phosphorylase (Bsel2056) belonging to glycoside hydrolase family 65 from Bacillus selenitireducens MLS10, which possesses synthetic ability for α-d-glucosyl disaccharides and trisaccharides through the reverse phosphorolysis with β-d-glucose 1-phosphate as the donor. Bsel2056 showed the flexibility for monosaccharide acceptors with alternative C2 substituent (2-amino-2-deoxy-d-glucose, 2-deoxy-d-arabino-hexose, 2-acetamido-2-deoxy-d-glucose, d-mannose), resulting in production of 1,4-α-d-glucosyl disaccharides with strict regioselectivity. In addition, Bsel2056 synthesized two maltose derivatives possessing additional d-glucosyl residue bound to C2 position of the d-glucose residue at the reducing end, 1,4-α-d-glucopyranosyl-[1,2-α-d-glucopyranosyl]-d-glucose and 1,4-α-d-glucopyranosyl-[1,2-β-d-glucopyranosyl]-d-glucose, from 1,2-α-d-glucopyranosyl-d-glucose (kojibiose) and 1,2-β-d-glucopyranosyl-d-glucose (sophorose), respectively, as the acceptors. These results suggested that Bsel2056 possessed a binding space to accommodate the bulky C2 substituent of d-glucose.

An expedient enzymatic route to isomeric 2-, 3- and 6-monodeoxy-monofluoro-maltose derivatives

2-Deoxy-2-fluoro-d-glucose, 3-deoxy-3-fluoro-d-glucose and 6-deoxy-6-fluoro-d-glucose were converted into the corresponding maltose derivatives using Arabidopsis thaliana DPE2-mediated trans-glycosylation reaction with glycogen acting as a glucosyl donor. 19F NMR spectroscopy proved to be a valuable tool for monitoring the progress of these reactions and to assess the nature of resulting oligomeric products.

Synthesis of fluorinated maltose derivatives for monitoring protein interaction by 19F NMR

A novel reporter system, which is applicable to the 19F NMR investigation of protein interactions, is presented. This approach uses 2-F-labeled maltose as a spy ligand to indirectly probe protein–ligand or protein–protein interactions of proteins fused or tagged to the maltose-binding protein (MBP). The key feature is the simultaneous NMR observation of both 19F NMR signals of gluco/manno-type-2-F-maltose-isomers; one isomer (α-gluco-type) binds to MBP and senses the protein interaction, and the nonbinding isomers (β-gluco- and/or α/β-manno-type) are utilized as internal references. Moreover, this reporter system was used for relative affinity studies of fluorinated and nonfluorinated carbohydrates to the maltose-binding protein, which were found to be in perfect agreement with published X-ray data. The results of the NMR competition experiments together with the established correlation between 19F chemical shift data and molecular interaction patterns, suggest valuable applications for studies of protein–ligand interaction interfaces.

Cholesteric star-shaped liquid crystals induced by a maltose core: synthesis and characteristics

Three esters of maltose (A1–A3) with 4–(4–(alkoxybenzoyloxy)phenoxy) –6–oxohexanoic acid (b1–b3) side-arms have been synthesised. All the maltose derivatives were laevo-rotationary, unlike their parent cores. The side arm b1 did not display liquid crystalline (LC) properties, and b2 and b3 displayed thermotropic nematic LC properties. The star-shaped compound (SSC) A1 with b1 side-arms did not display a mesomorphic phase. Unlike the nematic schlieren texture provided by side-arms b2 and b3, the star-shaped liquid crystals (SSLC) A2 and A3 displayed Grandjean and oily texture in the cholesteric phase. The results suggest that the LC properties of the side-arms have an important influence on the formation of LC properties in an SSC, and that the maltose core is important in determining the mesomorphic phase type. In other words, the SSC displayed LC properties only when the side-arms were also LC, and the maltose core induced a cholesteric phase in the SSLC with nematic side-arms. The mesomorphic regions for A2 and A3 were 39.1 and 53.7°C during the heating cycle and 63.8 and 107.0°C during the cooling cycle, respectively. The longer terminal chain rendered the mesomorphic region broader.

Electrochemical Characterisation of 6‐Iodomaltose, 6′‐Iodomaltose and 6‐Iodomaltotriose on a Silver Cathode and Their One‐Pot Electrochemical Dimerisation to New Mixed O/C Maltotetraose and Maltohexaose Mimics

The electrochemical reduction on silver of peracetylated 6-iodo-6-deoxy-beta-maltose (2), 6-iodo-6-deoxy-beta-maltotriose (3) and 6'-iodo-6'-deoxy-beta-maltose (4) has been investigated by cyclic voltammetry and performed on a preparative scale, according to the stoichiometry, -CH(2)I(2-4) + e(-) --> -CH(2)(*) + I(-). In agreement with the preparative electrolysis results, cyclic voltammetry showed different profiles for the reducing terminal-iodinated 2 and 3 and for the non-reducing terminal-iodinated 4. Compounds 2 and 3 partly dimerised to maltotetraoses mimics 7 (6,6-dimer) and 8 (5',5'-dimer) in 38% overall yield and to maltohexaose mimics 12 (6,6-dimer) and 13 (5',5'-dimer) in 30% overall yield, respectively. Compounds 7 and 12 came from the dimerisation of -CH(2)(*), primary radicals at C-6, which could also abstract H-5', becoming CH(3) and generating the C-5' quaternary radicals that dimerised in 8 and 13, respectively. These products were accompanied by the maltose derivatives 9, 10 and 11 a/b in 42% overall yield and by the maltotriose derivatives 14, 15 and 16 in 48% overall yield, respectively. Compounds 9, 14 and 10, 15 came from -CH(2)(*) disproportionation to CH(3) and CH(2)=C, respectively (exocyclic double bond C-6/C-5). Compounds 11 a/b and 16 came from C-5' radical reduction, followed by acetate anion elimination (double bonds C-6'/C-5' and C-5'/C-4'). In turn, 4 afforded only the 6',6'-dimer maltotetraose mimic 17 in 60% yield, accompanied by the reduced maltose 18 in 20% yield, in which the starting CH(2)I became CH(3). Compounds 7, 8, 12, 13 and 17 belong to a class of mixed O/C malto-mimic oligosaccharides wherein an unnatural C-C bond between two saccharide units increases metabolic stability compared to their O-analogues and modulates the sugar chain conformational flexibility, a fundamental parameter in determining protein-carbohydrate binding. Direct and spin-trapping EPR studies substantiated the radical-based nature of the dimerisation processes and allowed the identification of some of the paramagnetic species involved.

Maltose and Maltotriose Derivatives as Potential Inhibitors of the Maltose‐Binding Protein

AbstractInhibition of substrate binding to maltose‐binding protein (MBP) was investigated with structurally modified maltose and maltotriose derivatives that were designed based on the X‐ray analysis of maltose and maltotriose bound to MBP. In maltose, positions 1a, 2a, 2b, 4b and 6b were modified (compounds 1–3, 18a, b, 28a–c, 39 and 44) of which only the trivalent maltose derivatives 39 and 44 exhibited high affinity to MBP. Maltotriose modifications were carried out at position 6a and 6c (compounds 45–51). Compound 50, possessing a 6a‐O‐propyl group, and compound 51, where the 6c‐hydroxy group is replaced by bromide, showed higher affinity to MBP than the parent maltotriose. Hence, the structurally quite different compounds 39, 50 and 51 are important lead compounds for further studies. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Indirect and direct approaches in the synthesis of a new mono-6- O-benzyl methylated γ-cyclodextrin as chiral selector for enantioselective gas chromatography

6 I- O-Benzyl-2 I–VIII, 3 I–VIII, 6 II–VIII-tricosa- O-methyl-γ-cyclodextrin was synthesized using indirect and direct approaches. The first indirect strategy consists of a multi-step sequence including the ring opening of the permethylated α-cyclodextrin, elongation of the chain with a 6- O-benzyl methylated disaccharide derivative, and macrocyclization. The direct method deals with a selective mono-6- O-TBDMS protection, permethylation, deprotection, and benzylation sequence of γ-cyclodextrin. The results clearly show the higher efficiency of the direct approach but demonstrate the feasibility of the insertion of a modified maltose derivative (indirect method). The new mono-6-O-modified methylated γ-cyclodextrin was used as a selector for the preparation of the new chiral stationary phase. Preliminary enantioselective gas chromatography applications are also reported.

Production of a Thermoresistant Alpha-galactosidase from Thermus sp. Strain T2 for Food Processing

The gene of a thermostable alpha-galactosidase, aglA, from Thermus sp. strain T2 was sequenced, cloned and overexpressed in Escherichia coli (strain MC 2508. The purified enzyme proved to be quite thermostable, retaining high levels of activity even after incubation at 70°C. The optimal T was 65°C at pH 7. The highest activity was achieved at acid pH values, although good activity could be obtained in a broad pH range. Enzyme stability depends on the enzyme concentration at alkaline pH values, suggesting that under these conditions the subunit dissociation may be the first step in the inactivation of the enzyme. However, at pH 5 the enzyme stability becomes independent of the enzyme concentration. The enzyme also exhibited a quite broad specificity, although it shows the best activity with alpha derivatives of galactose, and was able to recognize very different substrates (alpha derivatives of mannose, xylose and maltose, and even beta galactose derivatives). There was no detectable activity against glucose derivatives.

Recovery of free oligosaccharides from derivatives labeled by reductive amination

This study examined chemical regeneration of free oligosaccharides from their fluorescent derivatives prepared by reductive amination with various aromatic amines. Maltose derivatives of ethyl 4-aminobenzoate ( p-ABEE), 2-aminobenzonitrile ( o-ABN), 4-aminobenzonitrile ( p-ABN), 7-amino-4-methylcoumarin (AMC), 2-aminobenzoic acid ( o-ABA), 2-aminobenzamide ( o-ABAD), 2-aminopyridine (AP), and 8-aminonaphthalene-1,3,6-trisulfonate (ANTS) were incubated at 30 °C with an aqueous solution of hydrogen peroxide/acetic acid. Recoveries of maltose from p-ABEE, p-ABN, and AMC derivatives were fairly good and gave approximately 90% of maltose. Recoveries of maltose from its o-substituted aniline ( o-ABA, o-ABAD, and o-ABN) derivatives were 5–40%, but maltose was unrecoverable from AP and ANTS derivatives. Nevertheless, prior treatment of an AP derivative with cyanogen bromide enabled the regeneration of maltose in high yields. As an application, p-ABEE-labeled N-glycans from some glycoproteins separated on an amide column were identified by converting peak components to their AP derivatives via free saccharides and following mapping by reversed-phase chromatography.

Synthesis and characterisation of novel chromogenic substrates for human pancreatic α-amylase

Derivatives of maltose and maltotriose were chemically synthesised as substrates for human pancreatic α-amylases and subjected to kinetic analysis. Rates measured were shown to reflect both hydrolysis and transglycosylation reactions. 4- O-Methylated derivatives of these substrates underwent only hydrolysis, thereby simplifying kinetic analyses. These modified substrates may be used for the detection and kinetic analysis of α-amylases, and are useful in rapidly screening for novel α-amylase inhibitors and for subsequent kinetic characterisation.

Synthesis, structural characterization, and antitumor activity of palladium(II) complexes containing a sugar unit

Six palladium(II) complexes as cisplatin derivatives with a sugar unit ( d-glucose, d-galactose, d-mannose, d-xylose, and maltose) have been prepared. The structural features of the complexes have been characterized by NMR spectroscopy, elemental analysis, mass spectroscopy, and X-ray crystallography. The complexes have been tested for in vivo cytotoxicity against P388 cells implanted in mice. All of Pd compounds are apparently nontoxic. A T/C value of 120% was obtained for maltose derivative at the dose of 400 mg/kg, which indicates that the compound may be endowed with antitumor activity.

The role of water in the design of glycosidic linkage flexibility

In this paper we show how a variety of computational methods are used to understand the role that water plays in the solution conformational dynamics of carbohydrates. A comparison is made between maltose and a designed disaccharide (α-D-Glc-NAc-(1→4)-β-D-Glc-3-NH2) in which the cross glycosidic linkage hydrogen bonds have been significantly strengthened. However, despite the stronger intramolecular hydrogen bonds in the maltose derivative, the correlation times for glycosidic dihedral angle fluctuations are approximately the same for the two sugars. Upon investigation of the water in the first hydration shells for the two disaccharides, high water probability densities were found between the functional groups straddling the glycosidic linkage that bonds the two monosaccharides together. This probability density corresponds to single water molecules forming bridging hydrogen bonds between the functional groups on either side of the linkage for periods of 3.66 ps in the case of maltose and 8.36 ps in the case of the amine derivative. Ab initio studies of saccharide structure interaction with single water molecules reveal that these intermolecular (sugar-solvent) hydrogen bonds are of similar strength to the intramolecular (sugar-sugar) hydrogen bonds. This combination of molecular dynamics and ab initio computational methods demonstrates that increasing the internal hydrogen bond strength in oligosaccharides does not lead to significantly slower internal molecular motion of these sugars in solution. The intermolecular hydrogen bonds formed with water compete equally with the intramolecular hydrogen bonds in the sugar. This result has important implications when considering hydrophobic versus hydrophilic effects in glycoproteins.