Determination of the structural integrity and stability of polysialic acid during alkaline and thermal treatment

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dc.identifier.uri http://dx.doi.org/10.15488/9903
dc.identifier.uri https://www.repo.uni-hannover.de/handle/123456789/9961
dc.contributor.author Bartling, Bastian
dc.contributor.author Rehfeld, Johanna S.
dc.contributor.author Boßmann, Daniel
dc.contributor.author de Vries, Ingo
dc.contributor.author Fohrer, Jörg
dc.contributor.author Lammers, Frank
dc.contributor.author Scheper, Thomas
dc.contributor.author Beutel, Sascha
dc.date.accessioned 2020-06-29T15:21:48Z
dc.date.available 2020-06-29T15:21:48Z
dc.date.issued 2020
dc.identifier.citation Bartling, B.; Rehfeld, J.S.; Boßmann, D.; De Vries, I.; Fohrer, J. et al.: Determination of the structural integrity and stability of polysialic acid during alkaline and thermal treatment. In: Molecules 25 (2020), Nr. 1, 165. DOI: https://doi.org/10.3390/molecules25010165
dc.description.abstract Polysialic acid (polySia) is a linear homopolymer of varying chain lengths that exists mostly on the outer cell membrane surface of certain bacteria, such as Escherichia coli (E. coli) K1. PolySia, with an average degree of polymerization of 20 (polySia avDP20), possesses material properties that can be used for therapeutic applications to treat inflammatory neurodegenerative diseases. The fermentation of E. coli K1 enables the large-scale production of endogenous long-chain polySia (DP ≈ 130) (LC polySia), from which polySia avDP20 can be manufactured using thermal hydrolysis. To ensure adequate biopharmaceutical quality of the product, the removal of byproducts and contaminants, such as endotoxins, is essential. Recent studies have revealed that the long-term incubation in alkaline sodium hydroxide (NaOH) solutions reduces the endotoxin content down to 3 EU (endotoxin units) per mg, which is in the range of pharmaceutical applications. In this study, we analyzed interferences in the intramolecular structure of polySia caused by harsh NaOH treatment or thermal hydrolysis. Nuclear magnetic resonance (NMR) spectroscopy revealed that neither the incubation in an alkaline solution nor the thermal hydrolysis induced any chemical modification. In addition, HPLC analysis with a preceding 1,2-diamino-4,5-methylenedioxybenzene (DMB) derivatization demonstrated that the alkaline treatment did not induce any hydrolytic effects to reduce the maximum polymer length and that the controlled thermal hydrolysis reduced the maximum chain length effectively, while costeffective incubation in alkaline solutions had no adverse effects on LC polySia. Therefore, both methods guarantee the production of high-purity, low-molecular-weight polySia without alterations in the structure, which is a prerequisite for the submission of a marketing authorization application as a medicinal product. However, a specific synthesis of low-molecular-weight polySia with defined chain lengths is only possible to a limited extent.
dc.language.iso eng
dc.publisher Basel : MDPI AG
dc.relation.ispartofseries Molecules 25 (2020), Nr. 1
dc.relation.uri https://doi.org/10.3390/molecules25010165
dc.rights CC BY 4.0 Unported
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.subject Endotoxin removal eng
dc.subject Hydrolysis eng
dc.subject NMR spectroscopy eng
dc.subject Polysialic acid eng
dc.subject Structure integrity eng
dc.subject.ddc 540 | Chemie ger
dc.title Determination of the structural integrity and stability of polysialic acid during alkaline and thermal treatment
dc.type article
dc.type Text
dc.relation.issn 1420-3049
dc.bibliographicCitation.issue 1
dc.bibliographicCitation.volume 25
dc.bibliographicCitation.firstPage 165
tib.accessRights frei zug�nglich


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