
Undergraduate Honors Theses
Thesis Defended
Spring 2018
Document Type
Thesis
Type of Thesis
Departmental Honors
Department
Chemistry & Biochemistry
First Advisor
Hang Hubert Yin
Second Advisor
Xuedong Liu
Third Advisor
Jeffrey Cameron
Fourth Advisor
Karolin Luger
Fifth Advisor
Pamela Harvey
Abstract
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.
Recommended Citation
Anderson, Rachel, "Application of the Sandmeyer Reaction Towards Synthesis of SelectiveToll-like Receptor 7 & 8 Antagonists" (2018). Undergraduate Honors Theses. 1547.
https://scholar.colorado.edu/honr_theses/1547