Sweet stability

Abstract: The disaccharide trehalose is known for its ability to stabilise proteins by preventing aggregation and elevating their denaturation temperature, consequently avoiding unfolding. The folding and function of proteins are vital for many biological processes. However, the underlying mechanisms of the stabilising effect of trehalose are not yet fully elucidated. A group of diseases known as amyloidosis is associated with the formation of amyloid fibrils, highly structured protein aggregates that can form in various tissues in the body. Enhancing our understanding of protein misfolding and the role of sugars in preventing amyloid fibril formation is therefore of great importance. In this thesis, the stabilising effect of trehalose is compared with that of sucrose, a structurally similar disaccharide. This comparison aims to solve unanswered questions regarding their interactions with proteins and surrounding water molecules. X-ray and neutron scattering confirmed that myoglobin is preferentially hydrated by water and revealed that trehalose slows down the dynamics of the protein to a greater extent than sucrose, with minimal direct interaction. Differential scanning calorimetry showed that both disaccharides increase the denaturation temperature of the protein lysozyme, sucrose slightly more than trehalose. Additionally, the glass transition temperature of trehalose is marginally higher. Small and wide-angle x-ray scattering demonstrated that both sugars inhibit amyloid fibril formation. The findings suggest that the effectiveness of both disaccharides in stabilising proteins varies with temperature; trehalose is more effective at lower temperatures around the glass transition, whereas sucrose may be slightly more efficient at higher temperatures around protein denaturation.

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