Multivalent, Stabilized Mannose‐6‐Phosphates for the Targeted Delivery of Toll‐Like Receptor Ligands and Peptide Antigens

• DOI: 10.1002/cbic.202000538
• Publication Date: 2020-08-31T02:27:05Z
• Authors: Niels R. M. Reint...; Elena Tondini; Christopher Vis; Toroa McGlinn; Nico J. Meeuwenoord; Tim P. Hogervorst; Herman S. Overkleeft; Dmitri V. Filippov; Gijsbert A. van d...; Ferry Ossendorp; Jeroen D. C. Codée
• Keywords: Mannose receptor; Conjugate; Mannose 6-phosphate

Abstract Mannose‐6‐phosphate (M6P) is recognized by the mannose‐6‐phosphate receptor and plays an important role in transport of cargo to endosomes, making it attractive tool improve endosomal trafficking vaccines. We describe herein assembly peptide antigen conjugates carrying clusters mannose‐6‐ C ‐phosphonates (M6Po). The M6Po's are stable M6P mimics that resistant cleavage phosphate group endogenous phosphatases. Two different strategies for incorporation M6Po conjugate have been developed: first relies on a “post‐assembly” click approach employing bearing alkyne functionality; second hinges ‐glycoside amino acid building block can be used solid‐phase synthesis. generated were further equipped with TLR7 ligand stimulate dendritic cell (DC) maturation. While presentation hindered presence clusters, leads increased activation DCs, thus demonstrating their potential improving vaccine adjuvanticity intraendosomally active TLR ligands.