Abstract by Teron Haynie
Chemistry and Biochemistry
Synthesis of candidate Natural Killer T cell ligands utilizing novel tandem Staudinger and aziridine formation reaction
Glycolipids interact with Natural Killer T cells (NKT cells) via the CD1D receptor, which triggers the role NKT cells play as the bridge between the adaptive and the innate immunities. Glycolipids have been thought to exist endogenously only in beta configurations in mammals, yet recent studies indicate that alpha glycolipids exist as well and can interact with NKT cells. The complete repertoire of endogenous NKT cells ligands has yet to be determined. Here we synthesize twelve novel NKT cell ligand candidates utilizing a novel tandem Staudinger and aziridine formation reaction. This reaction cyclizes a hydroxyl with an amine in a diastereoselective manner creating a new variant of glycosphingolipid. Based on our experience we propose that the endogenous ligand could be one of these heterocycle variants as we have observed cyclization of glycolipids under acidic conditions and it is probable that the biosynthetic pathway passes through the acidic lysosome. Our collaborators will test the NKT cell stimulatory profiles upon treatment with these compounds. We hope this information will aid in more efficacious vaccine development.