Heparin in Acid and Alkaline Environments—A Study of the Correlations between Hydrodynamic Properties and Desulphation

Author:

Kozlowski Aleksandra Maria1ORCID,Dinu Vlad2,MacCalman Thomas2,Smith Alan Mark1ORCID,Roubroeks Johannes Peter3ORCID,Yates Edwin Alexander4,Harding Stephen Ernest2ORCID,Morris Gordon Alistair1ORCID

Affiliation:

1. Biopolymer Research Centre, School of Applied Sciences, University of Huddersfield, Huddersfield HD1 3DH, UK

2. National Centre for Macromolecular Hydrodynamics, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Leicestershire LE12 5RD, UK

3. LEO Pharma A/S, Industriparken 55, 2750 Ballerup, Denmark

4. Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7ZB, UK

Abstract

This work evaluated the hydrodynamic properties of heparin hydrolysed at temperatures ranging from 40 °C to 80 °C in buffered acid and alkaline environments. The correlation between hydrodynamic parameters led to the conclusion that polymer conformational changes appeared to be minimal until chain depolymerisation, initiated at pH 1 and 80 °C. However, the synergy of conformational changes, even if minimal, and sulphate loss observed at pH 1, pH 3 and pH 12 (various temperatures) resulted in a loss of the antifactor Xa activity. Therefore, the ‘contribution’ of conformational changes should be added to the generally recognized effect of desulphation towards the activity of heparin. This is of significance as the processing of medical heparin is complex, and requires adjustment of several physical and chemical factors, including pH and temperature.

Publisher

MDPI AG

Subject

General Earth and Planetary Sciences,General Engineering,General Environmental Science

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