Synthesis of Sulfur and Amino 8-Substituted Adenine Derivatives as TLR7 Agonists

Toll-like receptors (TLRs) are a class of pattern recognition receptor (PRR) proteins, which play a vital role in the innate immune response. Upon recognition of microbial pathogens, TLRs initiate pathways which lead to the production of cytokines. For the past few years, TLR agonists have been used as adjuvants for vaccines against cancer, allergies, and viral infections. TLR7 agonists are of particular interest, as they can induce the production of interferons in plasmacytoid dendritic cells without stimulating the release of inflammatory cytokines. In this experiment, several sulfur and amino 8-substituted adenine molecules were synthesized for use as potential TLR7 agonists. Two of these compounds were tested for immunological activity at the Baylor Institute for Immunology Research in Dallas, and several others are still being developed.