Christina M. Othon; Francis W. Starr
Osmolytes are molecules capable of stabilizing solvated protein structures via modification of properties of water. Disaccharides molecules such as trehalose and sucrose appear to be excellent in protecting various biomolecules including proteins against wide range of environmental stress. Many organisms also utilize trehalose to survive the harsh environment around them, such as the tardigrade or grey tree frog. This property of trehalose has motivated widespread application of disaccharides in the cosmetic, pharmaceutical, and food industries. Although, a variety of studies have been done so far to clearly understand the mechanism behind this unique ability of trehalose, we are still far from reaching to any consensus on the action by which disaccharide molecules affect protein folding dynamics. This work will utilize multiple optical, spectroscopic, electronic and biophysical techniques to explore the modification of water and its effect on various model protein systems and will attempt to shed some light on mechanism of biopreservation by disaccharides osmolytes. We have demonstrated that a 10% slowdown in dynamics of water can impact the folding stability of various proteins such as BSA and Staph Nuclease. We demonstrated that preferential exclusion of sugars from the surface of proteins is an essential requirement for an osmolyte to be biopreservative in nature. We have also explored the destabilizing nature of a modified disaccharide sucralose for BSA and Staph Nuclease and presented a comparison with its counterpart Sucrose. We performed ligand docking simulations on four model protein systems to demonstrate that sucralose could directly interact with hydrophobic patches on surface of proteins. This direct interaction could be the mechanism by which it destabilizes the protein structures. To further understand the mechanism of biopreservation by disaccharides the role of glycosidic bond is also explored using three mono ring molecules glucose, methyl-α-d-glucopyranoside and myo-inositol. We also explored the effect of glucose ring opening in presence of water (reduction of sugars) on hydration dynamics and biopreservation of proteins.
Shukla, Nimesh, "Hydration Dynamics and its Impact on Osmoprotection by Disaccharide Osmolytes" (2018). Dissertations. 90.
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