Synthesis and Activity of 6″-Deoxy-6″-thio-α-GalCer and Peptide Conjugates

Authors: Compton, Benjamin J.; Tang, Ching-wen; Johnston, Karen A.; Osmond, Taryn L.; Hayman, Colin M.; Larsen, David S.; Hermans, Ian F.; Painter, Gavin F.; Organic Letters; (2015); 10.1021/acs.orglett.5b02836

A major challenge in the development of highly defined synthetic vaccines is the codelivery of vaccine components (i.e., antigen and adjuvant) to secondary lymphoid tissue to induce optimal immune responses. This problem can be addressed by synthesizing vaccines that comprise peptide antigens covalently attached to glycolipid adjuvants through biologically cleavable linkers. Toward this, a strategy utilizing previously unreported 6″-deoxy-6″-thio analogues of α-GalCer that can undergo chemoselective conjugation with peptide antigens is described. Administration of these conjugate vaccines leads to enhanced priming of antigen specific T cells. This simple vaccine design is broadly applicable to multiple disease indications such as cancer and infectious disease.