1. Lipopolysaccharide from Gut‐Associated Lymphoid‐Tissue‐Resident Alcaligenes faecalis: Complete Structure Determination and Chemical Synthesis of Its Lipid A.
- Author
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Shimoyama, Atsushi, Di Lorenzo, Flaviana, Yamaura, Haruki, Mizote, Keisuke, Palmigiano, Angelo, Pither, Molly D., Speciale, Immacolata, Uto, Tomoya, Masui, Seiji, Sturiale, Luisa, Garozzo, Domenico, Hosomi, Koji, Shibata, Naoko, Kabayama, Kazuya, Fujimoto, Yukari, Silipo, Alba, Kunisawa, Jun, Kiyono, Hiroshi, Molinaro, Antonio, and Fukase, Koichi
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CHEMICAL structure , *LIPID synthesis , *CHEMICAL synthesis , *LYMPHOID tissue , *TOLL-like receptors , *MYELOID differentiation factor 88 , *LIPOXINS - Abstract
Alcaligenes faecalis is the predominant Gram‐negative bacterium inhabiting gut‐associated lymphoid tissues, Peyer's patches. We previously reported that an A. faecalis lipopolysaccharide (LPS) acted as a weak agonist for Toll‐like receptor 4 (TLR4)/myeloid differentiation factor‐2 (MD‐2) receptor as well as a potent inducer of IgA without excessive inflammation, thus suggesting that A. faecalis LPS might be used as a safe adjuvant. In this study, we characterized the structure of both the lipooligosaccharide (LOS) and LPS from A. faecalis. We synthesized three lipid A molecules with different degrees of acylation by an efficient route involving the simultaneous introduction of 1‐ and 4′‐phosphates. Hexaacylated A. faecalis lipid A showed moderate agonistic activity towards TLR4‐mediated signaling and the ability to elicit a discrete interleukin‐6 release in human cell lines and mice. It was thus found to be the active principle of the LOS/LPS and a promising vaccine adjuvant candidate. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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