Type of Thesis
Chemistry & Biochemistry
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The first line of defense during infection relies on detecting the presence of pathogens and triggering pro-inflammatory responses by pattern recognition receptors (PRRs). Among PRRs, Toll-Like Receptors (TLRs) have been studied most extensively. TLRs are membrane receptors that recognize molecular patterns associated with pathogens and damaged cells to initiate immune responses. TLRs are good drug research targets because improper activation of TLRs has shown to be correlated with pathogenesis of various autoimmune diseases. TLR8 is an endogenous receptor that recognizes single-stranded RNA from viral infections. When TLR8 is improperly activated by self-RNAs, it can possibly lead to rheumatoid arthritis (RA) or other systemic autoimmune diseases such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and Sjögren's syndrome. The recently published study of Yin Lab and Shimizu Lab has revealed that the newly-identified TLR8 antagonists inhibit TLR8 signaling through a novel mechanism. An open space in the binding pocket with the TLR8 antagonists, CU-CPT9s, suggests that their structures can be optimized. Thus, this project investigated on further optimizing the molecular structure of CU-CPT9 to enhance the therapeutic values of potential TLR8 antagonists.
Koo, Kyoin, "Design and Synthesis of Toll-Like Receptor 8 Inhibitors: Optimizing the Potential Drugs for Autoimmune Diseases" (2018). Undergraduate Honors Theses. 1720.