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The heptose-deficient inner core of the lipopolysaccharide of several pathogenic strains of the Moraxellaceae family (Moraxella, Acinetobacter) and of Bartonella henselae, respectively, comprises an α-D-glucopyranose attached to position 5 of Kdo. In continuation of the synthesis of fragments of Acinetobacter haemolyticus LPS, the branched α-Glcp-(...
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... deprotection afforded the oli- gosaccharide ligands 16 (99%) and 19 (90%) in excellent yields. The 13 C NMR data of the oligosaccharide (Table 1) are in good agree- ment with the LPS-oligosaccharides isolated from B. henselae ATCC 49882 T* and A. haemolyticus, respectively. 9,10 Deviating assign- ments were only noted for C-7 of both Kdo units. ...
Context 2
... 3H, H-4, H-5′, H-7′), 3.91 (ddd, 1H, J4′,5′ 3.0 Hz, H-4′), 3.89-3.86 (m, 2H, H-8a, H-8′a), 3.85 (dd, 1H, J6″a,6″b 12.2, J6″a,5″ 2.6 Hz, H-6″), 3.78 (app t, 1H, J3″,4″ 9.2 Hz, H-3″), 3.665 (br d, 1H, J6′,7′ 7.5 Hz, H-6′), 3.66 (dd, 1H, J8′a,8′b 11.8, J7′,8′b 7.2 Hz, H-8′b), 3.58 (dd, 1H, J8b,8a 11.8, J8b,7 6.5 Hz, H-8b), 3.51 (app t, 1H, J5″,4″ 9.7 Hz, H-4″), 3.50 (br d, 1H, J6,7 9.5 Hz, H-6), 3.46 (dd, 1H, J2″,3″ 9.9 Hz, H-2″), 3.07 (s, 3H, OCH3), 2.05 (dd, 1H, J3′eq,3′ax 13.2, J3′eq,4′ 4.7 Hz, H-3′eq), 2.01 (dd, 1H, J3eq,3ax 12.6, J3eq,4 4.8 Hz, H-3eq), 1.94 (app t, 1H, J3ax,4 12.3 Hz, H-3ax), 1.75 (app t, 1H, J3′ax,4′ 12.7 Hz, H-3′ax); 13 C NMR (D2O, pD ~ 7.4): see Table 1; ESI-TOF HRMS: m/z = 657.1838; calcd for C23H38O20Na + : 657.1849. ...
Citations
... However, being linked to the 4-position in close vicinity to the 3,4,6-branched glucose structure in the 5-position, the second Kdo moiety might have an impact. The introduction of Kdo into synthetic targets complicates the synthesis, since Kdo is not commercially available but has to be synthesized in a multistep synthesis prior to its use in the oligosaccharide synthesis (Hansson & Oscarson, 2000), but methods have been developed to synthesise the αDGlc-(1 → 5)-[αKdo-(2 → 4)]-αKdo trisaccharide motif (Pokorny & Kosma, 2016). To investigate the impact of the (2 → 4)-linked Kdo residue on the conformation and the binding surface of the investigated oligosaccharide antigens molecular modelling studies were performed. ...
... Moraxellaceae family (order Pseudomonadales) was the majority and accounted for 11.1% in PMS. This family plays a major role in maintaining the glycolysis process (Pokorny and Kosma, 2016). The genus levels of Mycobacterium sp. ...
In this study, hydrogen harvesting from fermentation of sugarcane bagasse (SCB) was promoted by maintaining synergism between sulfonated graphene (SGR) catalyst and paper mill sludge (PMS). The sulfonic acid (–SO3H) groups in the catalyst played a major role in destructing the β-1,4 glycosidic bonds of sugarcane bagasse, releasing readily biodegradable sugars into the fermentation medium. The cellulose, hemicellulose, and lignin conversion efficiency were improved by 127.5%, 495.0%, and 109.2%, respectively with 20 mgSGR/gVS catalyst addition, compared with the control samples. These values were also higher than those obtained by non-sulfonated graphene catalyst. The hydrogenation of sugarcane bagasse was maximized at a sulfonated graphene catalyst dosage of 60 mgSGR/gVS, providing the highest hydrogen harvesting of 4104 ± 321 mL. This was associated with an increase of the Proteobacteria phyla up to 52.0%, Firmicutes phyla to 13.9%, and Acinetobacter sp. to 39.8% compared with only 37.0%, 11.3% and 11.1% in the control assay respectively. Moreover, sulfonated graphene catalyst supplementation promoted the acetate fermentation reaction pathway by increasing the acetate/butyrate ratio up to 4.1. Nevertheless, elevating the catalyst dosage up to 120 mgSGR/gVS reduced the hydrogen harvesting (1190 ± 92 mL) due to the release of furfural (1.76 ± 0.02 g/L) in the fermentation cultures, deteriorating the microbes’ internal composition and metabolism bioactivities. Finally maximizing the hydrogen productivity from sugarcane bagasse is feasible by incorporation of paper mill sludge and sulfonated graphene catalyst at dosage not exceeding 60 mgSGR/gVS. However, investigating the recyclability and disposal of digestate containing sulfonated graphene catalyst and the associated economic feasibility needs more attention in the future.
... Moraxella (Pokorny and Kosma 2016), ADP heptose is replaced by another sugar whereas some Gram-positive bacteria, like Streptomyces fimbriatus and Streptomyces hygroscopicus (Tang, Guo et al. 2018), are capable of synthesizing ADP heptose. ...
Eines der prävalentesten humanen Pathogene ist das Magenbakterium Helicobacter pylori, welches ca. die Hälfte der Weltbevölkerung infiziert. Die Persistenz geht mit einer chronischen Gastritis einher, welche bis zu Magenkrebs fortschreiten kann. H.pylori bedient sich diverser Mechanismen um sich der Erkennung des Immunsystems zu entziehen und somit eine chronische Infektion zu ermöglichen. Erhöhte Expression des Immunzellinhibitors PD-L1 wurde in Magenepithelzellen gefunden, welche mit diesem Gram-negativen Erreger infiziert wurden. In dieser Arbeit wurde die Regulation auf in vitro Ebene untersucht, wobei zwei unterschiedliche Mechanismen identifiziert wurden. Ursächlich für die frühe PD-L1-Induktion ist die ADP-heptose/ALPK1 Signalkaskade. Der bakterielle Metabolit ADP-heptose, welcher für die Bildung von LPS benötigt wird, wurde als PAMP identifiziert, welcher durch das Sekretionssystems cagT4SS in die infizierte transportiert und anschließend von der Host Kinase ALPK1 erkannt wird. Gegensätzlich hierzu, wurde festgestellt, dass die zweite PD-L1-Hochregulation auf der metabolischen Reprogrammierung des Wirts beruht. Ein Merkmal von H. pylori ist dessen Bedarf an Cholesterin, welches es aus dem Medium oder aus membranösen Lipidregionen des Wirts extrahiert wird. Es konnte bewiesen werden, dass dieser Sterol-Abbauprozess zu einer erhöhten Stoffwechselaktivität führt, die spezifisch mit einer Zunahme der Glykolyse verbunden ist und mit einer Expressionsverschiebung des ersten Glykolyseenzyms Hexokinase von der Isoform 1 zu 2 einhergeht. Knockdown und Knockout- Experimente wiesen auf einen Zusammenhang mit der Regulation des Immunzellinhibitoren PD-L1 hin.
... Interestingly, few exceptions exist. For instance, Moraxella [39], Rhizobium [40], Francisella [41], Legionella [42] and Brucella [43] do not possess the ADP-heptose synthetic pathway. In these, the heptose residues of the inner core are replaced by other sugars such as mannose [44] or glucose phosphate [45]. ...
The innate immune response constitutes the first line of defense against pathogens. It involves the recognition of pathogen-associated molecular patterns (PAMPs) by pathogen recognition receptors (PRRs), the production of inflammatory cytokines and the recruitment of immune cells to infection sites. Recently, ADP-heptose, a soluble intermediate of the lipopolysaccharide biosynthetic pathway in Gram-negative bacteria, has been identified by several research groups as a PAMP. Here, we recapitulate the evidence that led to this identification and discuss the controversy over the immunogenic properties of heptose 1,7-bisphosphate (HBP), another bacterial heptose previously defined as an activator of innate immunity. Then, we describe the mechanism of ADP-heptose sensing by alpha-protein kinase 1 (ALPK1) and its downstream signaling pathway that involves the proteins TIFA and TRAF6 and induces the activation of NF-κB and the secretion of inflammatory cytokines. Finally, we discuss possible delivery mechanisms of ADP-heptose in cells during infection, and propose new lines of thinking to further explore the roles of the ADP-heptose/ALPK1/TIFA axis in infections and its potential implication in the control of intestinal homeostasis.
Lipopolysaccharide (LPS) is a major virulence determinant in Gram-negative bacteria and responsible for many pathophysiological processes during bacterial infections. However, the accessibility of LPS-associated oligosaccharides for infectious mechanism study and vaccine development remains challenging. Herein, we report an efficiently stereocontrolled approach for synthesis of a common inner core trisaccharide containing difficult-to-access rare higher-carbon sugars heptose (Hep) and 3-deoxy-α-D-manno-oct-2-ulosonic acid (Kdo). Key features include comprehensive elaboration of practical synthesis of versatile Hep and Kdo building blocks and stereoselective assembly of an inner core trisaccharide from multiple pathogenic bacteria.
This review describes applications of radical reactions developed in the authors’ laboratory for the modification of carbohydrates. It focuses on tin‐free variation on the Barton‐McCombie deoxygenation; on reductive de‐iodination; on intermolecular radical additions of xanthates; on allylations and vinylations of xanthates and iodides, with emphasis on allylations using allylic alcohols activated as fluoropyridyl ethers; and, finally, on the synthesis of mercaptosugars. @font‐face {font‐family:"MS Mincho"; panose‐1:2 2 6 9 4 2 5 8 3 4; mso‐font‐alt:"ＭＳ 明朝"; mso‐font‐charset:128; mso‐generic‐font‐family:modern; mso‐font‐pitch:fixed; mso‐font‐signature:‐536870145 1791491579 134217746 0 131231 0;}@font‐face {font‐family:"Cambria Math"; panose‐1:2 4 5 3 5 4 6 3 2 4; mso‐font‐charset:0; mso‐generic‐font‐family:roman; mso‐font‐pitch:variable; mso‐font‐signature:‐536870145 1107305727 0 0 415 0;}@font‐face {font‐family:"Myriad Pro"; panose‐1:2 11 6 4 2 2 2 2 2 4; mso‐font‐alt:Corbel; mso‐font‐charset:0; mso‐generic‐font‐family:swiss; mso‐font‐pitch:variable; mso‐font‐signature:‐1610612049 1342185547 0 0 415 0;}@font‐face {font‐family:"\@MS Mincho"; panose‐1:2 2 6 9 4 2 5 8 3 4; mso‐font‐charset:128; mso‐generic‐font‐family:modern; mso‐font‐pitch:fixed; mso‐font‐signature:‐536870145 1791491579 134217746 0 131231 0;}p.MsoNormal, li.MsoNormal, div.MsoNormal {mso‐style‐unhide:no; mso‐style‐parent:""; margin:0cm; line‐height:150%; mso‐pagination:widow‐orphan; font‐size:8.0pt; mso‐bidi‐font‐size:12.0pt; font‐family:"Myriad Pro",sans‐serif; mso‐fareast‐font‐family:"MS Mincho"; mso‐bidi‐font‐family:"Times New Roman"; mso‐ansi‐language:DE; mso‐fareast‐language:JA;}p.Helv‐Abstract, li.Helv‐Abstract, div.Helv‐Abstract {mso‐style‐name:Helv‐Abstract; mso‐style‐unhide:no; mso‐style‐qformat:yes; margin‐top:6.0pt; margin‐right:0cm; margin‐bottom:6.0pt; margin‐left:0cm; text‐align:justify; text‐justify:inter‐ideograph; line‐height:150%; mso‐pagination:widow‐orphan; font‐size:8.0pt; mso‐bidi‐font‐size:10.0pt; font‐family:"Myriad Pro",sans‐serif; mso‐fareast‐font‐family:"MS Mincho"; mso‐bidi‐font‐family:"Times New Roman"; mso‐ansi‐language:EN‐US; mso‐fareast‐language:JA;}.MsoChpDefault {mso‐style‐type:export‐only; mso‐default‐props:yes; font‐size:10.0pt; mso‐ansi‐font‐size:10.0pt; mso‐bidi‐font‐size:10.0pt; mso‐fareast‐font‐family:"MS Mincho";}div.WordSection1 {page:WordSection1;}
The structural complexity of glycans poses a serious challenge in the chemical synthesis of glycosides, oligosaccharides and glycoconjugates. Glycan complexity, determined by composition, connectivity, and configuration far exceeds what nature achieves with nucleic acids and proteins. Consequently, glycoside synthesis ranks among the most complex tasks in organic synthesis, despite involving only a simple type of bond-forming reaction. Here, we introduce the fundamental principles of glycoside bond formation and summarize recent advances in glycoside bond formation and oligosaccharide synthesis.
There is an urgent need for new treatment options for carbapenem‐resistant Klebsiella pneumoniae (K. pneumoniae), which is a common cause of life‐threatening hospital‐ and community‐acquired infections. Prophylactic or therapeutic vaccination may offer an approach to control these infections, however, none has yet been approved for human use. Here, we report the chemical synthesis of an outer core tetra‐ and pentasaccharide derived from the lipopolysaccharide of K. pneumoniae. The oligosaccharides were equipped with an aminopentyl linker, which facilitated conjugation to the carrier proteins CRM197 and BSA. Mice immunized with the glycoconjugate vaccine candidates elicited antibodies that recognized isolated LPS as well as various strains of K. pneumoniae. The successful preparation of the oligosaccharides relied on the selection of monosaccharide building blocks equipped with orthogonal hydroxyl and amino protecting groups. It allowed the differentiation of three types of amines of the target compounds and the installation of a crowded 4,5‐branched Kdo moiety.
Acinetobacter baumannii is currently posing a serious threat to global health. Lipopolysaccharide (LPS) is a potent virulence factor of pathogenic Gram‐negative bacteria. To explore the antigenic properties of A. baumannii LPS, four Kdo‐containing inner core glycans from A. baumannii strain ATCC 17904 were synthesized. A flexible and divergent method based on the use of the orthogonally substituted α‐Kdo‐(2→5)‐Kdo disaccharides was developed. Selective removal of different protecting groups in these key precursors and elongation of sugar chain via α‐stereocontrolled coupling with 5,7‐O‐di‐tert‐butylsilylene or 5‐O‐benzoyl protected Kdo thioglycosides and 2‐azido‐2‐deoxyglucosyl thioglycoside allowed efficient assembly of the target molecules. Glycan microarray analysis of sera from infected patients revealed that the 4,5‐branched Kdo trimer was a potential antigenic epitope, which is attractive for further immunological research to develop carbohydrate vaccines against A. baumannii.
Acinetobacter baumannii is currently posing a serious threat to global health. Lipopolysaccharide (LPS) is a potent virulence factor of pathogenic Gram‐negative bacteria. To explore the antigenic properties of A. baumannii LPS, four Kdo‐containing inner core glycans from A. baumannii strain ATCC 17904 were synthesized. A flexible and divergent method based on the use of the orthogonally substituted α‐Kdo‐(2→5)‐Kdo disaccharides was developed. Selective removal of different protecting groups in these key precursors and elongation of sugar chain via α‐stereocontrolled coupling with 5,7‐ O ‐di‐ tert ‐butylsilylene or 5‐ O ‐benzoyl protected Kdo thioglycosides and 2‐azido‐2‐deoxyglucosyl thioglycoside allowed efficient assembly of the target molecules. Glycan microarray analysis of sera from infected patients revealed that the 4,5‐branched Kdo trimer was a potential antigenic epitope, which is attractive for further immunological research to develop carbohydrate vaccines against A. baumannii.
