@wsuchemistry.bsky.social (@waynestatechem.bsky.social)

The Nguyen lab has recently published a study in JACS Au, collaborating with Prof. Steve Varga at St. Jude Research Hospital, focused on the development of novel vaccine adjuvants, designed to enhance immune responses. #wsuchemistry #chembio #ChemSky #immunology doi.org/10.1021/jacs...

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Protonated Phenanthroline Catalyzed Stereoselective Glycosylation: Synthesis and Evaluation of Saponin Adjuvant Lablaboside F and Variants Leading to Simplified Vaccine Adjuvants Vaccine adjuvants are substances that are coadministered with antigens to enhance the immune response. Lablaboside F, a triterpene oleanolic acid β-linked to two trisaccharide chains on its eastern and western sides, emerged as a promising adjuvant candidate due to exhibiting robust adjuvanticity and low toxicity . We developed a β-stereoselective glycosylation method using a [PhenH]+[BF4]− catalyst to glycosylate oleanolic acid with C2-branched oligosaccharides, synthesizing lablaboside F and structural derivatives (S1–S8) as a result of constructing the target oligosaccharide. This approach simplifies the synthetic process when varying sugars are used and provides a platform for structure–activity relationship studies. Lablaboside F and S1–S8 were tested in vivo and in vitro for adjuvant activity, toxicity, and cytokine production. The entire branched trisaccharide on the western side of lablaboside F is not essential for adjuvant activity. Six derivatives showed low toxicity, while four increased pro-inflammatory cytokine levels. Notably, compound S5, composed of oleanolic acid and the eastern trisaccharide, demonstrated a favorable safety profile in vitro and higher antigen-specific total IgG levels than lablaboside F in vivo, without eliciting IgE production that can lead to allergic reactions. These findings advance our understanding of saponin structure–function relationships and provide a pathway for developing nontoxic adjuvants. https://doi.org/10.1021/jacsau.5c01046