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Title:Cholesterol Dynamics in Lipid Bilayers Revealed by NMR Spectroscopy
Author(s):Petros, Zoe A.
Contributor(s):Rienstra, Chad
Abstract:Solid-state nuclear magnetic resonance (SSNMR) is a spectroscopic technique that allows for the determination of structural features and dynamics of a wide variety of molecules. SSNMR is particularly well suited to study the structure of fibrillar and membrane proteins and small, lipophilic molecules. Cholesterol (Chol) is a sterol that comprises 50% of the lipid population of mammalian cell membranes and is critical for various biological processes. We are interested in studying cholesterol to understand its unique interactions with the antifungal drug amphotericin B (AmB). AmB is the gold standard for treatment of life-threatening systemic fungal infections; however, patients can experience severe nephrotoxicity. AmB’s dominant mode of action is the extraction of ergosterol from fungal cell membranes. Therefore, we hypothesize that AmB’s toxicity in mammalian cells is a result of the extraction of cholesterol from mammalian cell membranes. Using biosynthesized 13C-cholesterol, SSNMR and molecular dynamics simulations, we investigated the hierarchy of motions of membranous cholesterol. This work is the foundation of future studies involving AmB, to ultimately investigate the interaction between these two molecules. Understanding the interactions between AmB and cholesterol will allow us to improve the therapeutic index of this antifungal drug.
Issue Date:2017
Genre:Dissertation / Thesis
Rights Information:Copyright 2017 Zoe A. Petros
Date Available in IDEALS:2017-05-16

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