Automated solid phase synthesis of teichoic acids

Hogendorf, Wouter F. J.; Meeuwenoord, Nico J.; Overkleeft, Herman S.; Filippov, Dmitri V.; Laverde, Diana; Kropec, Andrea; Hüebner, Johannes; Marel, Gijsbert A. van der; Codée, Jeroen D. C.

doi:10.1039/c1cc13132j

Cited by 20 publications

(19 citation statements)

References 27 publications

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“…PhoR autophosphorylation is inhibited in vitro by Lipid φ.20 [20 (glycerol phosphate) subunits] but not by Lipid φ.1 [1 (glycerol phosphate) subunit] suggesting that the inhibitory activity resides in the poly(glycerol phosphate) moiety of the Lipid φ.20 analogue. This was investigated by testing the ability of synthetic poly(glycerol phosphate) polymers of 20 subunits to inhibit ′PhoR autophosphorylation in vitro (Hogendorf et al ., ). No inhibition of ′PhoR autophosphorylation was observed.…”

Section: Resultsmentioning

confidence: 97%

PhoR autokinase activity is controlled by an intermediate in wall teichoic acid metabolism that is sensed by the intracellular PAS domain during the PhoPR‐mediated phosphate limitation response of Bacillus subtilis

Botella

Devine

Hübner

et al. 2014

Molecular Microbiology

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SummaryThe PhoPR two-component signal transduction system controls one of the major responses to phosphate limitation in Bacillus subtilis. When activated it directs expression of phosphate scavenging enzymes, lowers synthesis of the phosphate-rich wall teichoic acid (WTA) and initiates synthesis of teichuronic acid, a non-phosphate containing replacement anionic polymer. Despite extensive knowledge of this response, the signal to which PhoR responds has not been identified. Here we report that one of the main functions of the PhoPR two-component system in B. subtilis is to monitor WTA metabolism. PhoR autokinase activity is controlled by the level of an intermediate in WTA synthesis that is sensed through the intracellular PAS domain. The pool of this intermediate generated by WTA synthesis in cells growing under phosphate-replete conditions is sufficient to inhibit PhoR autokinase activity. However WTA synthesis is lowered upon phosphate limitation by the combined effects of PhoP∼P-mediated activation of tuaA-H transcription and repression of tagAB. These transcriptional changes combine to lower the level of the inhibitory WTA metabolite thereby increasing PhoR autokinase activity. This amplifies the PHO response with full induction being achieved ∼ 90 min after the onset of phosphate limitation.

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Section: Resultsmentioning

confidence: 97%

PhoR autokinase activity is controlled by an intermediate in wall teichoic acid metabolism that is sensed by the intracellular PAS domain during the PhoPR‐mediated phosphate limitation response of Bacillus subtilis

Botella

Devine

Hübner

et al. 2014

Molecular Microbiology

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“…We, and others, have described a number of approaches to generate synthetic TA fragments 10 , including traditional solution phase studies 11 , light fluorous approaches 12 and fully automated solid phase 13 assemblies. All of our syntheses hinged on the use of well-established synthetic "DNA-chemistry", employing phosphoramidite building blocks bearing a dimethoxytrityl ether as a temporary protecting group for the nascent oligomer chain.…”

Section: Resultsmentioning

confidence: 99%

“…Supplementary data ( 1 H, 13 C, 31 P NMR spectra) associated with this article can be found, in the online version, at ...…”

Section: Supplementary Datamentioning

confidence: 99%

“…Column chromatography yielded intermediate 2-azido-4,6-di-O-benzyl-2-deoxy-3-O-napthyl-α/β-D-galactopyranose (0.64 g, 1.4 mmol) in >98% yield. TLC: R f 0.4 (30% EtOAc/pentane); IR (neat, cm -1 ): 3389,3059, 2916, 2868, 2108, 1096, 1059, 818, 746, 696; 1 H NMR (400 MHz, CDCl 3 ): δ= 7.80 - 7.01 (m, 29H),5.28 (d, J = 2.8 Hz, 1H), 10H), 1H), 4H), 1H), 2H), 1H), 1H), 1H);13 C NMR (101 MHz, CDCl 3 ): δ =…”

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confidence: 99%

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Synthesis of E. faecium wall teichoic acid fragments

Groenia

Laverde

et al. 2016

Bioorganic & Medicinal Chemistry

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The first synthesis of different Enterococcus faecium wall teichoic acid (WTA) fragments is presented. The structure of these major cell wall components was elucidated recently and it was shown that these glycerolphosphate (GroP) based polymers are built up from -6-(GalNAc-α(1-3)-GalNAc-β(1-2)-GroP)- repeating units. We assembled WTA fragments up to three repeating units in length, in two series that differ in the stereochemistry of the glycerolphosphate moiety. The key GalNAc-GalNAc-GroP synthons, required for the synthesis, were generated from galactosazide building blocks that were employed in highly stereoselective glycosylation reactions to furnish both the α- and β-configured linkages. By comparing the NMR spectra of the synthesized fragments with the isolated material it appears that the hereto undefined stereochemistry of the glycerol phosphate moiety is sn-glycerol-3-phosphate. The generated fragments will be valuable tools to study their immunological activity at the molecular level.

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“…56 Employing classical automated DNA synthesis, the aforementioned building blocks 102, 124 and 103 were used to generate the set of TAs depicted in Scheme 11. 56 Employing classical automated DNA synthesis, the aforementioned building blocks 102, 124 and 103 were used to generate the set of TAs depicted in Scheme 11.…”

Section: View Article Onlinementioning

confidence: 99%

Teichoic acids: synthesis and applications

Hogendorf

Overkleeft

et al. 2017

Chem. Soc. Rev.

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This review describes the developments in the synthesis of teichoic acids (TA) - glycosylated poly(alditolphosphates) - and the application of these fragments in immunological studies. These structurally diverse biopolymers are omnipresent constituents of the Gram-positive bacterial cell wall where they fulfill a variety of vital functions. They have been and continue to be attractive synthetic targets because of their challenging structures and the fact that their microheterogeneity precludes their isolation in single and pure enough form from natural sources. Progress in glycosylation chemistry and the development of effective phosphorylation chemistry has driven TA synthesis over the years, and highly complex and large TA structures can now reliably be targeted. Starting from the first TA synthesis in 1981, this review highlights the progress made in the field over the years. The synthesized TA fragments have been used to unravel their role in immunology and it is described how focused libraries of TAs have been used to discover the active principles of the TA polymers that interact with the innate immune system. Recently, synthetic TA fragments have also found applications as well-defined synthetic antigens for the generation of novel vaccine modalities to combat Gram-positive bacterial infections. It is foreseen that synthetic TA fragments will be valuable tools in the future to unravel the mode of action of these biomolecules at the molecular level. They will be instrumental in discovering and characterizing their designated biological binding partners, be it pattern recognition receptors or carbohydrate binding lectins or biomachinery enzymes. This review thus serves to showcase the potential of organic synthesis for (chemical) biology and immunology.

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Automated solid phase synthesis of teichoic acids

Cited by 20 publications

References 27 publications

PhoR autokinase activity is controlled by an intermediate in wall teichoic acid metabolism that is sensed by the intracellular PAS domain during the PhoPR‐mediated phosphate limitation response of Bacillus subtilis

PhoR autokinase activity is controlled by an intermediate in wall teichoic acid metabolism that is sensed by the intracellular PAS domain during the PhoPR‐mediated phosphate limitation response of Bacillus subtilis

Synthesis of E. faecium wall teichoic acid fragments

Teichoic acids: synthesis and applications

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