Extended Data Fig. 1: T785 synthesis, design and activity on pDCs.
a, b, Confirmation of T785 structure via (a) proton NMR and (b) LC-MS. c, Molecular docking studies using a co-crystal structure of human TLR8 and R848 (PDB ID: 3W3N) to visualize T785 in the binding pocket of TLR8 supported solvent accessibility of the point of conjugation. Zoomed in views of the binding pocket show solvent accessibility of the exit vector (upper panel) and a view of the entire TLR8 protein with a single T785 docked (lower panel). d, HEK293 Null reporter cells, the parental cell line used for hTLR7 and hTLR8 reporter cells, were stimulated overnight with a concentration titration of T785 or R848 and activity was measured using QuantiBlue detection medium. Data are shown from one independent experiment. e, pDCs were isolated from healthy donor blood and stimulated overnight with T785 (TLR7/8), R848 (TLR7/8) or CpG (TLR9). IFNα secretion was measured by ELISA. Data shown (mean and SEM) are from n=3 independent donors.
