Kinetics of insulin aggregation in aqueous solutions upon agitation in the presence of hydrophobic surfaces.
TLDR
The effects of agitation rate, interfacial interactions, and insulin concentration on the overall aggregation rate were examined, and mathematical modeling of proposed kinetic schemes was employed to identify possible reaction pathways and to explain greater stability at higher insulin concentration.Abstract:
The stability of protein-based pharmaceuticals (e.g., insulin) is important for their production, storage, and delivery. To gain an understanding of insulin's aggregation mechanism in aqueous solutions, the effects of agitation rate, interfacial interactions, and insulin concentration on the overall aggregation rate were examined. Ultraviolet absorption spectroscopy, high-performance liquid chromatography, and quasielastic light scattering analyses were used to monitor the aggregation reaction and identify intermediate species. The reaction proceeded in two stages; insulin stability was enhanced at higher concentration. Mathematical modeling of proposed kinetic schemes was employed to identify possible reaction pathways and to explain greater stability at higher insulin concentration.read more
Citations
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References
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Stability of Protein Pharmaceuticals
TL;DR: Current methodology to stabilize proteins is presented, including additives, excipients, chemical modification, and the use of site-directed mutagenesis to produce a more stable protein species.
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Stabilization of enzymes against thermal inactivation.
TL;DR: Developments in protein chemistry and the understanding of thermophily, along with sensible analyses of enzyme thermoinactivation and use of common sense will undoubtedly lead to many new approaches to stabilization of enzymes at high temperatures.
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Phenol stabilizes more helix in a new symmetrical zinc insulin hexamer
U. Derewenda,Zygmunt S. Derewenda,Eleanor J. Dodson,Guy Dodson,C. D. Reynolds,G. D. Smith,C. Sparks,D. C. Swenson +7 more
TL;DR: The structure of a new sym-metrical hexamer is reported, in which all six molecules have the B1–B8 helix seen in 4Zn-insulin, and Phenol molecules, found bonding specifi-cally to each molecule, evidently stabilize this new helical conformation.
Journal ArticleDOI
Reconstitution of lactic dehydrogenase. Noncovalent aggregation vs. reactivation. 1. Physical properties and kinetics of aggregation.
Journal ArticleDOI
Insulin aggregation in artificial delivery systems.
TL;DR: Serum apparently contains factor(s) that promote the dissolution of insulin and prevent the formation of peptide aggregates in dilute solutions, which will serve to decrease, but not eliminate, the problem of insulin aggregation in delivery systems.