Type of Thesis
Chemistry & Biochemistry
Hang Hubert Yin
Toll-like receptors (TLRs) are an important part of the innate immune system responsible for detecting signs of microbial invasion and cell damage and initiating the immune response. Overactivation of TLRs, presumably by inappropriate detection of endogenous ligands, has been linked to chronic inflammation and autoimmunity. Current therapeutics are broad-spectrum and inhibit the overall function of the immune system. In this work, a library of dual-TLR7/8 antagonists were prepared with the goal of engineering TLR7 specificity, then tested against HEK 293 cells expressing either TLR 7 or 8. An antagonist with IC50 0.22 ± 0.33 μM against TLR 8 and greater than 50 μM against TLR 7 is presented, which may find use as a therapeutic or chemical probe. While this demonstrates that engineering specificity is possible, further work is required to locate a TLR7-selective antagonist.
Anderson, Rachel, "Application of the Sandmeyer Reaction Towards Synthesis of SelectiveToll-like Receptor 7 & 8 Antagonists" (2018). Undergraduate Honors Theses. 1547.