Hydrolytic Degradation of Heparin in Acidic Environments: Nuclear Magnetic Resonance Reveals Details of Selective Desulfation

Kozlowski, Aleksandra M, Yates, Edwin A ORCID: 0000-0001-9365-5433, Roubroeks, Johannes P, Tommeraas, Kristoffer, Smith, Alan M and Morris, Gordon A (2021) Hydrolytic Degradation of Heparin in Acidic Environments: Nuclear Magnetic Resonance Reveals Details of Selective Desulfation. ACS APPLIED MATERIALS & INTERFACES, 13 (4). pp. 5551-5563.

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Official URL: http://dx.doi.org/10.1021/acsami.0c20198

Abstract

Heparin is a complex glycosaminoglycan, derived mainly from pig mucosa, used therapeutically for its anticoagulant activity. Yet, owing largely to the chain complexity, the progressive effects of environmental conditions on heparin structure have not been fully described. A systematic study of the influence of acidic hydrolysis on heparin chain length and substitution has therefore been conducted. Changes in the sulfation pattern, monitored <i>via</i> 2D NMR, revealed initial de-N-sulfation of the molecule (pH 1/ 40 °C) and unexpectedly identified the secondary sulfate of iduronate as more labile than the 6-O-sulfate of glucosamine residues under these conditions (pH 1/ 60 °C). Additionally, the loss of sulfate groups, rather than depolymerization, accounted for most of the reduction in molecular weight. This provides an alternative route to producing partially 2-O-de-sulfated heparin derivatives that avoids using conventional basic conditions and may be of value in the optimization of processes associated with the production of heparin pharmaceuticals.

Item Type:	Article
Uncontrolled Keywords:	heparin, acid stability, H-1 and 2D NMR, desulfation, hydrolytic degradation
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	14 Oct 2022 13:01
Last Modified:	07 Feb 2023 15:18
DOI:	10.1021/acsami.0c20198
Open Access URL:	https://pure.hud.ac.uk/en/publications/hydrolytic-...
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3165493