Synthesis and immunological evaluation of a low molecular weight saccharide with TLR-4 agonist activity

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• 作者：Vikram Basava^a ; Heather Romlein^b ; Constantine Bitsaktsis^b ; ; Cecilia H. Marzabadi^a ; ^{cecilia.marzabadi@shu.edu}
• 关键词：Agonist ; LPS ; Saccharide synthesis ; TLR-4 ; Innate immunity
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：25
• 期：2
• 页码：697-705
• 全文大小：1412 K
• 卷排序：25

文摘

The paucity of FDA approved adjuvants renders the synthesis, characterization, and use of new compounds as vaccine adjuvants, a necessity. For this purpose, a novel saccharide analog has been synthesized from glucosamine, pyruvylated galactose and 1,4-cyclohexanediol and its biological efficacy was determined in innate immune cells. More specifically, we assessed the production of pro-inflammatory cytokines from the murine monocyte cell line, Raw 264.7 and from C57 BL/6 mouse peritoneal macrophages following exposure to the saccharide analog. Our data conclude that the novel saccharide has immunostimulatory activity on mouse macrophages as indicated by the elevated levels of IL-6 and TNF-α in culture supernatants. This effect was TLR-4-dependent but TLR-2-independent. Our data, suggest TLR-4 agonism; a key feature of vaccine adjuvants.