A spoonful of sugar could be the medicine

Jung, Hea-Jin; Pamer, Eric G.

doi:10.1038/nature23084

Cited by 3 publications

(4 citation statements)

References 8 publications

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“…Once the molecular basis of these glycan-mediated bacteria-host interactions is revealed, it might be possible to refine the use of custom-designed glycan or lectin analogues, and specifically target the adhesins of pathogenic microbes in the oral cavity. Similar glyco-therapeutic approaches are already under investigation for other pathogens [260–262]. …”

Section: Perspectives For Use Of Glycans or Glycan-binding Molecules mentioning

confidence: 99%

Glycan recognition at the saliva – oral microbiome interface

Cross

Rühl

2018

Cellular Immunology

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The mouth is a first critical interface where most potentially harmful substances or pathogens contact the host environment. Adaptive and innate immune defense mechanisms are established there to inactivate or eliminate pathogenic microbes that traverse the oral environment on the way to their target organs and tissues. Protein and glycoprotein components of saliva play a particularly important role in modulating the oral microbiota and helping with the clearance of pathogens. It has long been acknowledged that glycobiological and glycoimmunological aspects play a pivotal role in oral host-microbe, microbe-host, and microbe-microbe interactions in the mouth. In this review, we aim to delineate how glycan-mediated host defense mechanisms in the oral cavity support human health. We will describe the role of glycans attached to large molecular size salivary glycoproteins which act as a first line of primordial host defense in the human mouth. We will further discuss how glycan recognition contributes to both colonization and clearance of oral microbes.

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Section: Perspectives For Use Of Glycans or Glycan-binding Molecules mentioning

confidence: 99%

Glycan recognition at the saliva – oral microbiome interface

Cross

Rühl

2018

Cellular Immunology

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“…5,8 For example, a mannose analogue was reported to be capable of inhibiting the adhesion and colonization of uropathogenic Escherichia coli in the gut by blocking the interaction of the adhesin FimH (a lectin) with glycosylated host proteins. 10 When combined with traditional antibiotics, these FimH antagonists also exhibited synergistic and more efficacious bacterial inhibitory activity, 11 making combination therapy an attractive strategy for the treatment of bacterial infection. Overall, the major approaches to effective inhibition of bacterial adhesion entail the use of small-molecule compounds to target specific adhesins and adhesion-based vaccines.…”

Section: Introductionmentioning

confidence: 99%

“…Bacterial colonization and subsequent infection are usually initiated by the adhesion of pathogenic bacteria to their host cells and tissues, a process mediated by adhesins-“adhesive” bacterial surface proteins or machinery interacting with host proteins. − Since compounds that block this process by antagonizing adhesins do not directly kill bacteria or inhibit their growth, the antiadhesion strategy significantly alleviates the increase in antibiotic resistance, thus attracting considerable recent interest as an effective approach to combat pathogen invasion. , For example, a mannose analogue was reported to be capable of inhibiting the adhesion and colonization of uropathogenic Escherichia coli in the gut by blocking the interaction of the adhesin FimH (a lectin) with glycosylated host proteins . When combined with traditional antibiotics, these FimH antagonists also exhibited synergistic and more efficacious bacterial inhibitory activity, making combination therapy an attractive strategy for the treatment of bacterial infection.…”

Section: Introductionmentioning

confidence: 99%

Configuration-Specific Antibody for Bacterial Heptosylation: An Antiadhesion Therapeutic Strategy

Liao

et al. 2022

J. Am. Chem. Soc.

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Alternative antibacterial therapies refractory to existing mechanisms of antibiotic resistance are urgently needed. One such attractive therapy is to inhibit bacterial adhesion and colonization. Ser O-heptosylation (Ser O-Hep) on autotransporters of Gram-negative bacteria is a novel glycosylation and has been proven to be essential for bacterial colonization. Herein, we chemically synthesized glycopeptides containing this atypical glycan structure and an absolute C6 configuration through the assembly of Ser O-Hep building blocks. Using glycopeptides as haptens, we generated first-in-class poly-and monoclonal antibodies, termed Anti-Ser Hep1a and Anti-Ser Hep1b , that stereoselectively recognize Ser O-heptosylation (D/L-glycero) with high specificity in vitro and in vivo. Importantly, these antibodies effectively blocked diffusely adhering Escherichia coli 2787 adhesion to HeLa cells and in mice in a dose-and Ser O-Hep-dependent manner. Together, these antibodies represent not only useful tools for the discovery of unknown serine O-heptosylated proteins bearing various C6 chiral centers but also a novel class of antiadhesion therapeutic agents for the treatment of bacterial infection.

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“…Consequently, they have become a focus theme in biochemistry and synthetic targets for pharmaceutical studies. [1][2][3][4][5][6][7][8][9] Among the various reactions available for the synthesis of glycoconjugates, the Ferrier rearrangement is an important reaction for the synthesis of 2,3-unsaturated glycosides. 10 The products of this transformation are versatile chiral intermediates for the synthesis of a variety of important biologically active compounds and natural products.…”

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confidence: 99%

A Highly Efficient Magnetic Iron(III) Nanocatalyst for Ferrier Rearrangements

Dong¹,

Ding²,

Guo³

et al. 2019

Synlett

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A novel and highly efficient magnetic Fe3O4@C@Fe(III) core–shell catalyst, in which the carbon shell was prepared from lotus leaf, was fabricated. This nanocatalyst was successfully applied in the synthesis of a series of 2,3-unsaturated O-glycosides in excellent yields and with high selectivity, especially in the case of 2-halo O-glycosides, which differ in reactivity from nonsubstituted O-glycosides, but which have scarcely been explored before. Moreover, the catalyst could be easily separated from the reaction by the application of an external magnetic force and reused a minimum of five times without any significant decrease in the yields of the products. In addition, the reaction proceeded readily on a gram scale, which provides a bright prospect for future applications.

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A spoonful of sugar could be the medicine

Abstract: Pili are filamentous bacterial structures that promote adhesion to host cells. It emerges that a small molecule that inhibits this adhesion can prevent colonization of the mouse gut by a pathogenic bacterium.

Cited by 3 publications

References 8 publications

Glycan recognition at the saliva – oral microbiome interface

Glycan recognition at the saliva – oral microbiome interface

Configuration-Specific Antibody for Bacterial Heptosylation: An Antiadhesion Therapeutic Strategy

A Highly Efficient Magnetic Iron(III) Nanocatalyst for Ferrier Rearrangements

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