TY - JOUR
T1 - Hydrolytic Degradation of Heparin in Acidic Environments
T2 - Nuclear Magnetic Resonance Reveals Details of Selective Desulfation
AU - Kozlowski, Aleksandra
AU - Yates, Edwin
AU - Roubroeks, Johannes
AU - Tømmeraas, Kristoffer
AU - Smith, Alan
AU - Morris, Gordon
N1 - Publisher Copyright:
©
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/2/3
Y1 - 2021/2/3
N2 - 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.
AB - 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.
KW - heparin
KW - acid stability
KW - 1H and 2D NMR
KW - desulfation
KW - hydrolytic degradation
KW - H and 2D NMR
UR - http://www.scopus.com/inward/record.url?scp=85100252856&partnerID=8YFLogxK
U2 - 10.1021/acsami.0c20198
DO - 10.1021/acsami.0c20198
M3 - Article
VL - 13
SP - 5551
EP - 5563
JO - ACS applied materials & interfaces
JF - ACS applied materials & interfaces
SN - 1944-8244
IS - 4
ER -