The biopharmaceutical industry has been growing at a tremendous rate, with sales of ;Chapter 1 of this dissertation focuses on background information and explains the role of disulfide bonds in proteins, their advantages and limitations and different degradation pathways. Research objective and specific aims are also outlined in Chapter 1. Model hGH-derived tryptic peptides were used to investigate reaction mechanism and kinetics in aqueous solution (Chapter 2). RP-HPLC was used as a quantitative tool and product identity was further confirmed on the LC-MS. The effects of pH, temperature, oxidation suppressants and peptide secondary structure on thiol-disulfide exchange were also explored.;Protein drugs are also manufactured as lyophilized powders to improve stability and retain potency during storage. In Chapter 3 of this dissertation, thiol-disulfide exchange during lyophilization and storage in the solid state using model peptides are discussed. Comparisons are drawn to the aqueous solution studies in Chapter 2. We also investigated the effect of factors that may contribute to thiol-disulfide exchange during lyophilization and these include; initial peptide concentration, temperature, buffer type and concentration, length of primary drying time and peptide adsorption to ice.;In Chapter 4, thiol-disulfide exchange in intact hGH was investigated to understand the effects of higher-order structure on reaction kinetics. Free thiol containing peptides of different length and sequence and GSH were used to facilitate thiol-disulfide exchange in intact hGH and hGH-derived peptides with a disulfide bond. Finally, concluding remarks, future perspectives and implications for protein formulations are discussed in Chapter 5.
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