The Role of Mono and Disaccharides in Solubilizing and Enhancing Insulin Stability
Disciplines
Biochemistry
Abstract (300 words maximum)
Over the past 20 years, the FDA has approved 894 therapeutic proteins, which include 354 monoclonal antibodies and 85 peptides or polypeptides, representing a significant advancement in the biomedical industry. However, the complexity of these treatments presents serious stability challenges during storage. Issues such as deamidation, oxidation, aggregation, and disulfide shuffling can jeopardize their efficacy and safety. Insulin, a peptide hormone essential for glucose homeostasis, must maintain its structural integrity to remain biologically active in therapeutic formulations. However, its stability is influenced by environmental factors such as cosolvent, pH, and temperature, which may unfold and destabilize its native structure. Previous studies showed that both glucose and sucrose play important roles in stabilizing proteins; however, sucrose stands out as the more effective choice. The mechanism behind this enhanced stabilization lies in sucrose's ability to increase solvent crowding around the protein. This crucial interaction significantly boosts the protein's stability, especially at elevated temperatures, making sucrose an indispensable ingredient for maintaining protein integrity in various applications. This study investigates how different mono and disaccharides such as glucose, lactose, sucrose, and maltose affect insulin’s folding and stability. To assess the stability of Insulin, various samples of Insulin are prepared in water and in solutions containing mono and disaccharides. High resolution mass spectrometry was used to monitor the folding, unfolding and adduct formation of Insulin in the presence of mono and disaccharides. The results indicate that glucose does not form any adduct with insulin, suggesting it does not interfere with insulin’s structure and may help preserve its stability. Sucrose exhibited the highest level of adduct formation with insulin, with nine sucrose adducts are noticed with insulin. Lactose and maltose demonstrated a similar adduct formation pattern but to a lesser extent. Our preliminary results showed that disaccharides may not be suitable for Insulin and peptide stabilization.
Academic department under which the project should be listed
CSM - Chemistry and Biochemistry
Primary Investigator (PI) Name
Mohammad Halim
The Role of Mono and Disaccharides in Solubilizing and Enhancing Insulin Stability
Over the past 20 years, the FDA has approved 894 therapeutic proteins, which include 354 monoclonal antibodies and 85 peptides or polypeptides, representing a significant advancement in the biomedical industry. However, the complexity of these treatments presents serious stability challenges during storage. Issues such as deamidation, oxidation, aggregation, and disulfide shuffling can jeopardize their efficacy and safety. Insulin, a peptide hormone essential for glucose homeostasis, must maintain its structural integrity to remain biologically active in therapeutic formulations. However, its stability is influenced by environmental factors such as cosolvent, pH, and temperature, which may unfold and destabilize its native structure. Previous studies showed that both glucose and sucrose play important roles in stabilizing proteins; however, sucrose stands out as the more effective choice. The mechanism behind this enhanced stabilization lies in sucrose's ability to increase solvent crowding around the protein. This crucial interaction significantly boosts the protein's stability, especially at elevated temperatures, making sucrose an indispensable ingredient for maintaining protein integrity in various applications. This study investigates how different mono and disaccharides such as glucose, lactose, sucrose, and maltose affect insulin’s folding and stability. To assess the stability of Insulin, various samples of Insulin are prepared in water and in solutions containing mono and disaccharides. High resolution mass spectrometry was used to monitor the folding, unfolding and adduct formation of Insulin in the presence of mono and disaccharides. The results indicate that glucose does not form any adduct with insulin, suggesting it does not interfere with insulin’s structure and may help preserve its stability. Sucrose exhibited the highest level of adduct formation with insulin, with nine sucrose adducts are noticed with insulin. Lactose and maltose demonstrated a similar adduct formation pattern but to a lesser extent. Our preliminary results showed that disaccharides may not be suitable for Insulin and peptide stabilization.