Small‐Molecule Carbohydrate‐Based Immunostimulants

Marzabadi, Cecilia H.; Franck, Richard W.

doi:10.1002/chem.201601539

Cited by 22 publications

(24 citation statements)

References 133 publications

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“…To summarize, in this study a new lipid A structure from C. psychrerythraea 34H was characterized; it enlarges the number of structure–activity relationships necessary for the design of new immunomodulatory molecules …”

Section: Discussionmentioning

confidence: 99%

Unusual Lipid A from a Cold‐Adapted Bacterium: Detailed Structural Characterization

et al. 2017

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Colwellia psychrerythraea 34H is a Gram-negative cold-adapted microorganism that adopts many strategies to cope with the limitations associated with the low temperatures of its habitat. In this study, we report the complete characterization of the lipid A moiety from the lipopolysaccharide of Colwellia. Lipid A and its partially deacylated derivative were completely characterized by high-resolution mass spectrometry, NMR spectroscopy, and chemical analysis. An unusual structure with a 3-hydroxy unsaturated tetradecenoic acid as a component of the primary acylation pattern was identified. In addition, the presence of a partially acylated phosphoglycerol moiety on the secondary acylation site at the 3-position of the reducing 2-amino-2-deoxyglucopyranose unit caused tremendous natural heterogeneity in the structure of lipid A. Biological-activity assays indicated that C. psychrerythraea 34H lipid A did not show an agonistic or antagonistic effect upon testing in human macrophages.

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Section: Discussionmentioning

confidence: 99%

Unusual Lipid A from a Cold‐Adapted Bacterium: Detailed Structural Characterization

et al. 2017

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“…We will discuss examples involving chemical modifications of the carbohydrates, especially the covalent conjugates of antigens and carbohydrate-based delivery carrier or adjuvants. Vaccines that contain carbohydrates and derivatives only as antigen components, or natural carbohydrates encapsulated/admixed with other vaccine components, have been reviewed (Marzabadi and Franck, 2017;Colombo et al, 2018;Wei et al, 2018;Weyant et al, 2018;Jin et al, 2019;Micoli et al, 2019), and are not discussed here.…”

Section: Introductionmentioning

confidence: 99%

Carbohydrate Conjugates in Vaccine Developments

Lang

Huang

2020

Front. Chem.

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Vaccines are powerful tools that can activate the immune system for protection against various diseases. As carbohydrates can play important roles in immune recognition, they have been widely applied in vaccine development. Carbohydrate antigens have been investigated in vaccines against various pathogenic microbes and cancer. Polysaccharides such as dextran and β-glucan can serve as smart vaccine carriers for efficient antigen delivery to immune cells. Some glycolipids, such as galactosylceramide and monophosphoryl lipid A, are strong immune stimulators, which have been studied as vaccine adjuvants. In this review, we focus on the current advances in applying carbohydrates as vaccine delivery carriers and adjuvants. We will discuss the examples that involve chemical modifications of the carbohydrates for effective antigen delivery, as well as covalent antigen-carbohydrate conjugates for enhanced immune responses.

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“…The most well-studied glycolipid antigen is α-galactosylceramide (α-O-GalCer), also called KRN 7000, which has been tested in several mouse models of disease and in a limited number of human trials. 9,10,11,12 However, clinical applications of KRN 7000 have been stymied; the consensus of the immunology community is that it is handicapped by its inability to induce a clear Th1/Th2 cytokine bias. In this context C - KRN 7000, the C -glycoside analog in which the glycoside oxygen is replaced with a “CH 2 ”, emerged as a benchmark Th1 biased molecule in mice, inducing high levels of IFN-γ and IL-12 with negligible levels of IL-4.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and biological activities of C-glycosides of KRN 7000 with novel ceramide residues

Altiti

Zhang

et al. 2017

Carbohydrate Research

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The identification of immunoactive agents for clinical and mechanistic applications is a very active area of research. In this vein, analogues of the potent immunostimulant KRN 7000 with diverse cytokine profiles have attracted considerable attention. Herein, we report on the synthesis and activity for four new C-glycosides of KRN 7000, 11-phenylundecanoyl and 11-p-fluorophenylundecanoyl derivatives of C-KRN 7000, 2,3-bis-epi-C-KRN 7000 and the reverse amide of C-KRN 7000. In mice, compared to C-KRN 7000, 2,3-bis-epi-C-KRN 7000 stimulated higher release of the anti-inflammatory cytokine IL-4 and lower release of the inflammatory cytokines IFN-γ and IL-12. The phenyl terminated alkanoyl and reverse amide analogues were inactive. These data suggest that structure activity effects for KRN 7000 are not necessarily additive and their use in the design of new analogues will require an improved understanding of how subtle structural changes impact on cytokine activity.

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Small‐Molecule Carbohydrate‐Based Immunostimulants

Cited by 22 publications

References 133 publications

Unusual Lipid A from a Cold‐Adapted Bacterium: Detailed Structural Characterization

Unusual Lipid A from a Cold‐Adapted Bacterium: Detailed Structural Characterization

Carbohydrate Conjugates in Vaccine Developments

Synthesis and biological activities of C-glycosides of KRN 7000 with novel ceramide residues

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