Effect of polyols on the conformational stability and biological activity of a model protein lysozyme |
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Authors: | Singh Somnath Singh Jagdish |
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Affiliation: | (1) Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, 58105 Fargo, ND;(2) Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University Medical Center, Omaha, NE |
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Abstract: | The purpose of this study was to investigate the stabilizing action of polyols against various protein degradation mechanisms (eg, aggregation, deamidation, oxidation), using a model protein lysozyme. Differential scanning calorimeter (DSC) was used to measure the thermodynamic parameters, mid point transition temperature and calorimetric enthalpy, in order to evaluate conformational stability. Enzyme activity assay was used to corroborate the DSC results. Mannitol, sucrose, lactose, glycerol, and propylene glycol were used as polyols to stabilize lysozyme against aggregation, deamidation, and oxidation. Mannitol was found to stabilize lysozyme against aggregation, sucrose against deamidation both at neutral pH and at acidic pH, and lactose against oxidation. Stabilizers that provided greater conformational stability of lysozyme against various degradation mechanisms also protected specific enzyme activity to a greater extent. It was concluded that DSC and bioassay could be valuable tools for screening stabilizers in protein formulations. |
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Keywords: | differential scanning calorimeter protein conformational stability polyols enzyme activity assay lysozyme |
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