The Structure–Activity Relationship and Anticoagulation Mechanism of Polyglycerol Sulfates of Different Architectures

Authored by

Clemens Krage, Marie Weinhart, Benjamin F. L. Lai, Anja Stöshel, Katharina Achazi, Jayachandran N. Kizhakkedathu, Rainer Haag

Abstract

Although unfractionated heparin (UFH) remains a vital agent for rapid anticoagulation, its reliance on animal-derived sources results in batch-to-batch variability and contamination risks, and its clinical application is further restricted by the possibility of heparin-induced thrombocytopenia. Dendritic polyglycerol sulfates were investigated as heparin analogues in 2004 due to their ability to mimic its charge, which is essential for its acting mechanism, and revealed an anticoagulant activity of 15–35% compared to UFH. In the current study, we found that the anticoagulant effect of polyglycerol sulfates further increases with their flexibility, resulting in a comparable activity of linear polyglycerol sulfate to UFH. Furthermore, we comprehensively analyzed the mechanism of action and discovered an antithrombin-independent, thrombin-selective mechanism. Moreover, we confirmed that FDA-approved protamine sulfate is a viable reversal agent for polyglycerol sulfate.

Details

Organisation(s): Institute of Physical Chemistry and Electrochemistry
Section Polymers and Biomaterials
External Organisation(s): Freie Universität Berlin (FU Berlin)
University of British Columbia
Type: Article
Journal: BIOMACROMOLECULES
Volume: 27
Pages: 3367–3375
No. of pages: 9
ISSN: 1525-7797
Publication date: 11.05.2026
Publication status: Published
Peer reviewed: Yes
ASJC Scopus subject areas: Bioengineering, Biomaterials, Polymers and Plastics, Materials Chemistry
Sustainable Development Goals: SDG 3 - Good Health and Well-being
Electronic version(s): https://doi.org/10.1021/acs.biomac.6c00308 (Access: Open )