Monitoring the stability of heparin: NMR evidence for the rearrangement of sulfated iduronate in phosphate buffer.

Autor: Kozlowski AM; Biopolymer Research Centre, School of Applied Sciences, University of Huddersfield, HD1 3DH Huddersfield, United Kingdom. Electronic address: aleksandra.kozlowski@chalmers.se., Yates EA; Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7ZB, United Kingdom. Electronic address: e.a.yates@liverpool.ac.uk., Roubroeks JP; LEO Pharma A/S, Industriparken 55, 2750 Ballerup, Denmark. Electronic address: sjru@novonordisk.com., Tømmeraas K; LEO Pharma A/S, Industriparken 55, 2750 Ballerup, Denmark. Electronic address: ktqr@novonordisk.com., Larsen FH; LEO Pharma A/S, Industriparken 55, 2750 Ballerup, Denmark. Electronic address: fxldk@leo-pharma.com., Smith AM; Biopolymer Research Centre, School of Applied Sciences, University of Huddersfield, HD1 3DH Huddersfield, United Kingdom. Electronic address: a.m.smith@hud.ac.uk., Morris GA; Biopolymer Research Centre, School of Applied Sciences, University of Huddersfield, HD1 3DH Huddersfield, United Kingdom. Electronic address: g.morris@hud.ac.uk.
Jazyk: angličtina
Zdroj: Carbohydrate polymers [Carbohydr Polym] 2023 May 15; Vol. 308, pp. 120649. Date of Electronic Publication: 2023 Feb 03.
DOI: 10.1016/j.carbpol.2023.120649
Abstrakt: Heparin, a major anticoagulant drug, comprises a complex mixture of motifs. Heparin is isolated from natural sources while being subjected to a variety of conditions but the detailed effects of these on heparin structure have not been studied in depth. Therefore, the result of exposing heparin to a range of buffered environments, ranging pH values from 7 to 12, and temperatures of 40, 60 and 80 °C were examined. There was no evidence of significant N-desulfation or 6-O-desulfation in glucosamine residues, nor of chain scission, however, stereochemical re-arrangement of α-L-iduronate 2-O-sulfate to α-L-galacturonate residues occurred in 0.1 M phosphate buffer at pH 12/80 °C. The results confirm the relative stability of heparin in environments like those during extraction and purification processes; on the other hand, the sensitivity of heparin to pH 12 in buffered solution at high temperature is highlighted, providing an important insight for heparin manufacturers.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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