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Insight into human insulin aggregation revisited using NMR derived translational diffusion parameters

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dc.abstract.enThe NMR derived translational diffusion coefficients were performed on unlabeled and uniformly labeled 13C,15N human insulin in water, both in neat, with zinc ions only, and in pharmaceutical formulation, containing only m-cresol as phenolic ligand, glycerol and zinc ions. The results show the dominant role of the pH parameter and the concentration on aggregation. The diffusion coefficient Dav was used for monitoring the overall average state of oligomeric ensemble in solution. The analysis of the experimental data of diffusion measurements, using the direct exponential curve resolution algorithm (DECRA) allows suggesting the two main components of the oligomeric ensemble. The 3D HSQC-iDOSY, (diffusion ordered HSQC) experiments performed on 13C, 15N-fully labeled insulin at the two pH values, 4 and 7.5, allow for the first time a more detailed experimental observation of individual components in the ensemble. The discussion involves earlier static and dynamic laser light scattering experiments and recent NMR derived translational diffusion results. The results bring new informations concerning the preparation of pharmaceutical formulation and in particular a role of Zn2+ ions. They also will enable better understanding and unifying the results of studies on insulin misfolding effects performed in solution by diverse physicochemical methods at different pH and concentration.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorŁukasiewicz, Natalia
dc.contributor.authorPłucienniczak, Grażyna
dc.contributor.authorSokołowska, Iwona
dc.contributor.authorBocian, Wojciech
dc.contributor.authorKozerski, Lech
dc.contributor.authorBednarek, Elżbieta
dc.contributor.authorBorowicz, Piotr
dc.contributor.authorSitkowski, Jerzy
dc.contributor.authorKoźmiński, Wiktor
dc.contributor.authorUrbańczyk, Mateusz
dc.date.accessioned2024-01-25T04:19:47Z
dc.date.available2024-01-25T04:19:47Z
dc.date.issued2018
dc.description.financeNie dotyczy
dc.description.number2
dc.description.volume71
dc.identifier.doi10.1007/S10858-018-0197-Y
dc.identifier.issn0925-2738
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/109367
dc.identifier.weblinkhttps://link.springer.com/article/10.1007%2Fs10858-018-0197-y
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofJournal of Biomolecular NMR
dc.relation.pages101-114
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.subject.enNMR of 13C 15N enriched insulin
dc.subject.enpH dependence of insulin aggregation
dc.subject.enMonitoring aggregation by NMR derived diffusion coefficient Dav
dc.titleInsight into human insulin aggregation revisited using NMR derived translational diffusion parameters
dc.typeJournalArticle
dspace.entity.typePublication