title: Synthesis and immunological evaluation of a low molecular weight saccharide with TLR-4 agonist activity.
abstract: 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.
authors.affiliation: Department of Chemistry & Biochemistry, Seton Hall University, 400 South Orange Ave., South Orange, NJ 07079, USA.
authors.forename: Vikram
authors.initials: V
authors.lastname: Basava
authors.affiliation: Department of Biological Science, Seton Hall University, 400 South Orange Ave., South Orange, NJ 07079, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Romlein
authors.affiliation: Department of Biological Science, Seton Hall University, 400 South Orange Ave., South Orange, NJ 07079, USA.
authors.forename: Constantine
authors.initials: C
authors.lastname: Bitsaktsis
authors.affiliation: Department of Chemistry & Biochemistry, Seton Hall University, 400 South Orange Ave., South Orange, NJ 07079, USA. Electronic address: cecilia.marzabadi@shu.edu.
authors.forename: Cecilia H
authors.initials: CH
authors.lastname: Marzabadi
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D007114:Immunization; D008070:Lipopolysaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D008970:Molecular Weight; D000067996:RAW 264.7 Cells; D013329:Structure-Activity Relationship; D051197:Toll-Like Receptor 4 / Q000819:agonists* / Q000276:immunology*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4
keywords: Agonist; Innate immunity; LPS; Saccharide synthesis; TLR-4