Design and Synthesis of Cationic Steroid Antimicrobial Compounds, Synthesis of Glycolipids Recognized by Natural Killer T Cells and Development of TLR-1, TLR-6 Heterodimer Binders and Studies of Their Immunology Activities
Cationic steroid antimicrobial agents (CSAs) are a family of bile acid derivatives. These compounds are amphiphilic and mimic endogenous antimicrobial peptides. The antimicrobial activities of CSA-13 have been investigated and due to portent bactericidal activities and low toxicity, a large amount of CSA-13 is demanded for clinic trails and other antimicrobial applications. During our studies, we optimized the synthetic route of CSA-13, so that it can be prepared at the kilogram, even in tons scale. We investigated three routes and one of them is suitable for industry, because only recrystallization is needed in the synthesis. Natural killer T cells (NKT cells) are a kind of lymphocyte that bridge the adaptive immune system with the innate immune system. Once stimulated by glycolipids, NKT cells influence immune responses. To search for better glycolipid ligands, scientists have isolated many natural products to get inspiration. Thrautochysides A-C was isolated from a group of marine protists. These compounds have an interesting structure on their sphingosine lipid chains. We finished the iii synthesis of thraustochyside B, and made substantial progress toward the synthesis of thraustochyside A. Toll like receptors (TLRs) are integral components of the innate immune system. They recognize antigens and induce dendritic cells to give immune responses. TLR1, TLR2 and TLR6 recognize lipopetides, and these TLRs function as heterodimers. TLR1/TLR2 dimer recognition gives inflammatory responses, and TLR2/TLR6 dimer recognition gives immunomodulatory responses. We used modeling of TLRs to find a compound, which can fill the lipid binding pockets of the TLR2 and TLR6 dimer. In our study, we found the peptide chain of the antigen Pam2CSK4 can be replaced by a water soluble polyamine, which confirmed the function of the peptide to increase the water solubility.
College and Department
Physical and Mathematical Sciences; Chemistry and Biochemistry
BYU ScholarsArchive Citation
Feng, Yanshu, "Design and Synthesis of Cationic Steroid Antimicrobial Compounds, Synthesis of Glycolipids Recognized by Natural Killer T Cells and Development of TLR-1, TLR-6 Heterodimer Binders and Studies of Their Immunology Activities" (2011). Theses and Dissertations. 2751.
Synthesis, Cationic steroid antimicrobial, glycolipids, TLR-1, TLR-6, Immunology