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41.
Robert M. Archer Dr. Sylvain F. Royer William Mahy Dr. Caroline L. Winn Prof. Michael J. Danson Dr. Steven D. Bull 《Chemistry (Weinheim an der Bergstrasse, Germany)》2013,19(8):2895-2902
Practical syntheses of 2‐keto‐3‐deoxy‐D ‐xylonate (D ‐KDX) and 2‐keto‐3‐deoxy‐L ‐arabinonate (L ‐KDA) that rely on reaction of the anion of ethyl 2‐[(tert‐butyldimethylsilyl)oxy]‐2‐(dimethoxy phosphoryl) acetate with enantiopure glyceraldehyde acetonide, followed by global deprotection of the resultant O‐silyl‐enol esters, have been developed. This has enabled us to confirm that a 2‐keto‐3‐deoxy‐D ‐gluconate aldolase from the archaeon Sulfolobus solfataricus demonstrates good activity for catalysis of the retro‐aldol cleavage of both these enantiomers to afford pyruvate and glycolaldehyde. The stereochemical promiscuity of this aldolase towards these enantiomeric aldol substrates confirms that this organism employs a metabolically promiscuous pathway to catabolise the C5‐sugars D ‐xylose and L ‐arabinose. 相似文献
42.
Huiqing Li Dr. Kai‐For Mo Dr. Qun Wang Dr. C. Kendall Stover Dr. Antonio DiGiandomenico Prof. Geert‐Jan Boons 《Chemistry (Weinheim an der Bergstrasse, Germany)》2013,19(51):17425-17431
Pseudomonas aeruginosa is an opportunistic Gram‐negative bacterium that can cause life‐threatening infections in critically ill and cystic fibrosis patients. The Psl exopolysaccharide of P. aeruginosa offers an attractive serotype‐independent antigen for the development of immunotherapies. Here, the first chemical synthesis of a panel of oligosaccharides derived from the exopolysaccharide of P. aeruginosa by a synthetic strategy that efficiently deals with the stereoselective installation of several β‐mannosides and the formation of a mannoside that is extended by saccharide moieties at C‐1, C‐2, and C‐3 in a crowded 1,2,3‐cis configuration is described. The approach was employed to prepare tetra‐, penta‐, and hexa‐ and decasaccharide part structures. The compounds were employed to define the epitope requirements of several functionally active monoclonal antibodies (mAbs) that can bind three distinct epitopes of Psl (class I, II, and III). The class II mAb reacted potently with each oligosaccharide indicating its epitope resides within the tetrasaccharide and does not require the branched mannoside of Psl. The class III antibody did not bind the tetra‐ or pentasaccharide; however, it did react potently with the hexasaccharide and weakly with the decasaccharide, suggesting a terminal glucoside is required for optimal binding. Unexpectedly, the class I mAb did not bind any of the oligosaccharides indicating that Psl contains a yet to be elucidated sub‐stoichiometric isoform. This study demonstrates that functional activity of a mAb does not only depend on the avidity of binding but also on the location of an epitope within a bacterial polysaccharide. The results also provide a strong impetus to analyze further the structure of Psl to identify the class I epitope, that is expected to provide an attractive target for the development of a synthetic vaccine for P. aeruginosa. 相似文献
43.
Dipl.‐Chem. Christian Pett M. Sc. Manuel Schorlemer Dr. Ulrika Westerlind 《Chemistry (Weinheim an der Bergstrasse, Germany)》2013,19(50):17001-17010
By displaying different O‐glycans in a multivalent mode, mucin and mucin‐like glycoproteins are involved in a plethora of protein binding events. The understanding of the roles of the glycans and the identification of potential glycan binding proteins are major challenges. To enable future binding studies of mucin glycan and glycopeptide probes, a method that gives flexible and efficient access to all common mucin core‐glycosylated amino acids was developed. Based on a convergent synthesis strategy starting from a shared early stage intermediate by differentiation in the glycoside acceptor reactivity, a common disaccharide building block allows for the creation of extended glycosylated amino acids carrying the mucin type‐2 cores 1–4 saccharides. Formation of a phenyl‐sulfenyl‐N‐Troc (Troc=trichloroethoxycarbonyl) byproduct during N‐iodosuccinimide‐promoted thioglycoside couplings was further characterized and a new methodology for the removal of the Troc group is described. The obtained glycosylated 9‐fluorenylmethoxycarbonyl (Fmoc)‐protected amino acid building blocks are incorporated into peptides for multivalent glycan display. 相似文献
44.
Monosaccharides and disaccharides are important dietary components, but if insufficiently metabolized by some population subgroups, they are also linked to disease patterns. Thus, the correct analytical identification, quantification, and labeling of these food components are crucial to inform and potentially protect consumers. Enzymatic assays and high-performance anion-exchange chromatography with pulsed amperometric detection are established methods for the quantification of monosaccharides and disaccharides that, however, require long measuring times (60–180 min). Accelerated methods for the identification and quantification of the nutritionally relevant monosaccharides and disaccharides d -glucose, d -galactose, d -fructose, sucrose, lactose, and maltose were therefore developed. To realize this goal, the NMR experiments HSQC (heteronuclear single quantum coherence) and acceleration by sharing adjacent polarization (ASAP)-HSQC were applied. Measurement times were reduced to 27 and 6 min, respectively, by optimizing the interscan delay and applying non-uniform sampling. The optimized methods were used to quantify d -glucose, d -galactose, d -fructose, sucrose, and lactose in various dairy products. Results of the HSQC and ASAP-HSQC methods are equivalent to the results of the reference methods in terms of both precision and accuracy, demonstrating that these methods can be used to correctly analyze nutritionally relevant monosaccharides and disaccharides in short times. 相似文献
45.
Dr. Gordon Jacob Boehlich Hannes Sterzel Prof. Dr. Julia Rehbein Ass. Prof. Dr. Nina Schützenmeister 《Chemistry (Weinheim an der Bergstrasse, Germany)》2022,28(71):e202202619
Due to their high stability towards enzymatic hydrolysis C-acyl glycosidic compounds are useful synthetic intermediates for potential candidates in drug discovery. Syntheses for C-acyl mannosides have remained scarce and usually employ donors obtained from lengthy syntheses. Furthermore, syntheses of unprotected C-acyl mannosides have not been reported so far, due to the incapability of the C-acyl mannoside motif with deprotection conditions for protective groups commonly used in carbohydrate chemistry. Herein, we report an efficient and highly α-selective four-step one-pot method for the synthesis of C-acyl α-d -manno-, l -rhamno- and d -lyxopyranosides from easily accessible persilylated monosaccharides and dithianes requiring only trace amounts of a copper source as catalyst and explain the crucial role of the catalyst by mechanistic studies. Furthermore, the C-acyl α-glycosides were easily isomerized to give rapid access to their β-anomers. 相似文献
46.
Dr. Santiago Alonso-Gil Dr. Kamil Parkan Dr. Jakub Kaminský Dr. Radek Pohl Dr. Takatsugu Miyazaki 《Chemistry (Weinheim an der Bergstrasse, Germany)》2022,28(14):e202200148
The conformational changes in a sugar moiety along the hydrolytic pathway are key to understand the mechanism of glycoside hydrolases (GHs) and to design new inhibitors. The two predominant itineraries for mannosidases go via OS2→B2,5→1S5 and 3S1→3H4→1C4. For the CAZy family 92, the conformational itinerary was unknown. Published complexes of Bacteroides thetaiotaomicron GH92 catalyst with a S-glycoside and mannoimidazole indicate a 4C1→4H5/1S5→1S5 mechanism. However, as observed with the GH125 family, S-glycosides may not act always as good mimics of GH's natural substrate. Here we present a cooperative study between computations and experiments where our results predict the E5→B2,5/1S5→1S5 pathway for GH92 enzymes. Furthermore, we demonstrate the Michaelis complex mimicry of a new kind of C-disaccharides, whose biochemical applicability was still a chimera. 相似文献
47.
Robert Lassfolk Manuel Pedrón Prof. Tomás Tejero Prof. Pedro Merino Johan Wärnå Prof. Reko Leino 《Chemistry (Weinheim an der Bergstrasse, Germany)》2022,28(34):e202200499
Acyl group migration affects the synthesis, isolation, manipulation and purification of all acylated organic compounds containing free hydroxyl groups, in particular carbohydrates. While several isolated studies on the migration phenomenon in different buffers have been reported, comprehensive insights into the overall migration process in different monosaccharides under similar conditions have been lacking. Here, we have studied the acyl migration in different monosaccharides using five different acyl groups by a combination of experimental, kinetic and theoretical tools. The results show that the anomeric configuration in the monosaccharide has a major influence on the migration rate, together with the relative configurations of the other hydroxyl groups and the nature of the migrating acyl group. Full mechanistic model, based on computations, demonstrates that the acyl migration proceeds through an anionic stepwise mechanism with linear dependence on the [OH−] and the pKa of the hydroxyl group toward which the acyl group is migrating. 相似文献
48.
Gabriella Kervefors Kumar Bhaskar Pal Gergely L. Tolnai Mukul Mahanti Hakon Leffler Ulf J. Nilsson Berit Olofsson 《Helvetica chimica acta》2021,104(2):e2000220
β-Galactose derivatives have recently been reported to selectively inhibit galectin-3, and a library of O3-arylated galactosides with varying substitution patterns was designed to study such inhibitions further. The O3-arylated galactosides were synthesized using diaryliodonium salts under mild and transition metal free conditions, providing the target products in moderate to good yields. An O3-trifluoroethylated galactoside was also synthesized using iodonium salt chemistry. Azido-substituted products were subsequently transformed into the corresponding triazoles. After deprotection, a selection of galactoside derivatives were evaluated for inhibitory potencies against galectins-1, 3, 4 N (N-terminal domain), 4 C (C-terminal domain), 7, 8 N, 8 C, 9 N, and 9 C and one compound with promising affinity and selectivity for both the N- and C-terminal domain of galectin-9 was discovered. 相似文献
49.
Matthias Krumb Dr. Maximilian Jäger Alice Voss Loreen Immig Dr. Karin Peters Danuta Kowalczyk Prof. Dr. Albrecht Bufe Prof. Dr. Till Opatz Prof. Dr. Otto Holst Prof. Dr. Christian Vogel Dr. Marcus Peters 《Chemistry (Weinheim an der Bergstrasse, Germany)》2021,27(3):928-933
Arabinogalactan, a microheterogeneous polysaccharide occurring in plants, is known for its allergy-protective activity, which could potentially be used for preventive allergy treatment. New treatment options are highly desirable, especially in a preventive manner, due to the constant rise of atopic diseases worldwide. The structural origin of the allergy-protective activity of arabinogalactan is, however, still unclear and isolation of the polysaccharide is not feasible for pharmaceutical applications due to a variation of the activity of the natural product and contaminations with endotoxins. Therefore, a pentasaccharide partial structure was selected for total synthesis and subsequently coupled to a carrier protein to form a neoglycoconjugate. The allergy-protective activity of arabinogalactan could be reproduced with the partial structure in subsequent in vivo experiments. This is the first example of a successful simplification of arabinogalactan with a single partial structure while retaining its allergy-preventive potential. 相似文献
50.
Dr. R. Fernando Martínez Zilei Liu Dr. Andreas F. G. Glawar Dr. Akihide Yoshihara Prof. Ken Izumori Prof. George W. J. Fleet Dr. Sarah F. Jenkinson 《Angewandte Chemie (International ed. in English)》2014,53(4):1160-1162
The scarcity and expense of access to L ‐sugars and other rare sugars have prevented the exploitation of their biological potential; for example D ‐psicose, only recently available, has been recognized as an important new food. Here we give the definitive and cheap synthesis of 99.4% pure L ‐glucose from D ‐glucose which requires purification of neither intermediates nor final product other than extraction into and removal of solvents; a simple crystallization will raise the purity to >99.8%. 相似文献