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

Aleksandra Kozlowski, Edwin Yates, Johannes Roubroeks, Kristoffer Tømmeraas, Alan Smith, Gordon Morris

Research output: Contribution to journalArticlepeer-review

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 via 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.
Original languageEnglish
Pages (from-to)5551-5563
Number of pages13
JournalACS Applied Materials and Interfaces
Volume13
Issue number4
Early online date20 Jan 2021
DOIs
Publication statusPublished - 3 Feb 2021

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