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.

Antimicrobial peptides (AMPs) are ubiquitous and display broad-spectrum antimicrobial activity that can control bacterial colonization of surfaces. Ceragenins are small-molecule mimics of AMPs and have several advantages over AMPs, including cost of manufacture and stability. A ceragenin, CSA-120, modified with an acrylamide group was directly incorporated into fluoropolymer coatings as a means of inhibiting bacterial biofilm formation. The ceragenin-containing coatings displayed improved performance. By conjugating a copper chelating group to the ceragenin, chelation of 64Cu by the conjugate was effective and provided a stable complex that allowed in vivo imaging. This conjugate may provide a means of identifying infection sites in patients presenting general signs of infection without localized symptoms. A combination nanoparticle comprised of a maghemite core for enhanced T2 MRI contrast diagnostics, a colloidal silver shell acting as an antimicrobial and therapeutic vehicle, and a ceragenin (CSA- 124) surfactant providing microbial adhesion was synthesized and characterized by multiple methods. Silver nanoparticles conjugated with ceragenin, CSA-124, as a potential Gram-positiveselective antimicrobial were synthesized and termed as CSA-SNPs. Herein, CSA-SNPs are characterized using multiple methods and the antimicrobial properties are determined through minimum inhibitory concentration/minimum bactericidal concentration (MIC/MBC) and time-kill study. Prostanoids are a natural subclass of eicosanoids generated mainly from metabolic oxidation of arachidonic acid. Cyclopentenone prostaglandins (cyPGs) contain a highly reactive α,β-unsaturated carbonyl group in their cyclopentenone ring and possess three main potentially therapeutic properties: anti-inflammatory, antiproliferative and antiviral. We designed and synthesized EC and its derivatives in reducing secretion of pro-inflammatory cytokines IL-6 and IL-12. Mucosal-Associated Invariant T (MAIT) Cells are unique innate-like T cells and play a key role in host defense against bacterial and fungal infection as well as in human autoimmune diseases. The MAIT cells are activated through T-cell receptor αβ chain (TCR-αβ) binding with the MR1-ligand, which is vitamin B metabolites presented on MR1. Rribityllumazines, one of important MR1-ligand was synthesized in my study.