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Title
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Nonhydrolyzable heptose bis- and monophosphate analogues modulate pro-inflammatory TIFA-NF-kappa B signaling
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Author
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Abstract
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| d-Glycero-d-manno-heptose-1 beta,7-bisphosphate (HBP) andd-glycero-d-manno-heptose-1 beta-phosphate (H1P) are bacterial metabolites that were recently shown to stimulate inflammatory responses in host cells through the activation of the TIFA-dependent NF-kappa B pathway. To better understand structure-based activity in relation to this process, a family of nonhydrolyzable phosphonate analogues of HBP and H1P was synthesized. The inflammation modulation by which these molecules induce the TIFA-NF-kappa B signal axis was evaluatedin vivoat a low-nanomolar concentration (6 nM) and compared to that of the natural metabolites. Our data showed that three phosphonate analogues had similar stimulatory activity to HBP, whereas two phosphonates antagonized HBP-induced TIFA-NF-kappa B signaling. These results open new horizons for the design of pro-inflammatory and innate immune modulators that could be used as vaccine adjuvant. |
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Language
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English
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Source (journal)
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ChemBioChem: a European journal of chemical biology. - Weinheim
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Publication
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Weinheim
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Wiley-v c h verlag gmbh
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2020
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ISSN
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1439-4227
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DOI
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10.1002/CBIC.202000319
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Volume/pages
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p. 1-10
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ISI
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000544743000001
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Pubmed ID
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32452604
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Full text (Publisher's DOI)
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Full text (open access)
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Full text (publisher's version - intranet only)
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