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Design and Synthesis of Ceragenins–Cationic Steroid Antimicrobial Compounds, Structural Improvement and Synthesis of Cyclopentenone Prostaglandins and Modification and Synthesis of Derivatives of Ribityllumazines: Potential Antigens for Activation of MAIT Cells

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.

Identiferoai:union.ndltd.org:BGMYU2/oai:scholarsarchive.byu.edu:etd-9283
Date01 April 2019
CreatorsLi, Yubo
PublisherBYU ScholarsArchive
Source SetsBrigham Young University
Detected LanguageEnglish
Typetext
Formatapplication/pdf
SourceTheses and Dissertations
Rightshttp://lib.byu.edu/about/copyright/

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