TY - JOUR
T1 - Peptides conjugated to 2-alkoxy-8-oxo-adenine as potential synthetic vaccines triggering TLR7
AU - Gential, Geoffroy P.P.
AU - Hogervorst, Tim P.
AU - Tondini, Elena
AU - Graaff, Michel J. van de
AU - Overkleeft, Herman S.
AU - Codée, Jeroen D.C.
AU - Marel, Gijsbert A. van der
AU - Ossendorp, Ferry
AU - Filippov, Dmitri V.
PY - 2019/3
Y1 - 2019/3
N2 - Covalent linking of immunogenic oligopeptides with synthetic Toll-like receptor ligands is a useful approach to develop self-adjuvanting vaccines. In particular, small-molecule based agonists of Toll-like receptor 7 (TLR7) that are derived from 8-oxo-adenine core are potentially promising because these chemically robust TLR7 ligands can be connected to peptide T-cell epitopes via straightforward solid-phase peptide synthesis. In this contribution we present the synthesis of a Boc-protected 9-benzyl-2-alkoxy-8-oxo-adenine building block and its application in the online solid phase synthesis of three peptide conjugates that differ in the position of the TLR7 ligand within the peptide. The conjugates are able to induce dendritic cell maturation and T cell proliferation while the position of the ligand impacts T cell proliferation potency.
AB - Covalent linking of immunogenic oligopeptides with synthetic Toll-like receptor ligands is a useful approach to develop self-adjuvanting vaccines. In particular, small-molecule based agonists of Toll-like receptor 7 (TLR7) that are derived from 8-oxo-adenine core are potentially promising because these chemically robust TLR7 ligands can be connected to peptide T-cell epitopes via straightforward solid-phase peptide synthesis. In this contribution we present the synthesis of a Boc-protected 9-benzyl-2-alkoxy-8-oxo-adenine building block and its application in the online solid phase synthesis of three peptide conjugates that differ in the position of the TLR7 ligand within the peptide. The conjugates are able to induce dendritic cell maturation and T cell proliferation while the position of the ligand impacts T cell proliferation potency.
UR - https://doi.org/10.1016/j.bmcl.2019.03.048
U2 - 10.1016/j.bmcl.2019.03.048
DO - 10.1016/j.bmcl.2019.03.048
M3 - Article
SN - 0960-894X
VL - 29
SP - 1340
EP - 1344
JO - Bioorganic & Medicinal Chemistry Letters
JF - Bioorganic & Medicinal Chemistry Letters
IS - 11
ER -