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Issue 6, 2019, Issue in Progress

The neutralization of heparan sulfate by heparin-binding copolymer as a potential therapeutic target

Author affiliations

Abstract

Besides regulating ligand–receptor and cell–cell interactions, heparan sulfate (HS) may participate in the development of many diseases, such as cancer, bacterial or viral infections, and their complications, like bleeding or inflammation. In these cases, the neutralization of HS could be a potential therapeutic target. The heparin-binding copolymer (HBC, PEG41-PMAPTAC53) was previously reported by us as a fully synthetic compound for efficient and safe neutralization of heparins and synthetic anticoagulants. In a search for molecular antagonists of HS, we examined the activity of HBC as an HS inhibitor both in vitro and in vivo and characterized HBC/HS complexes. Using a colorimetric Azure A method, isothermal titration calorimetry and dynamic light scattering techniques we found that HBC binds HS by forming complexes below 200 nm with less than 1 : 1 stoichiometry. We confirmed the HBC inhibitory effect in rats by measuring activated partial thromboplastin time, prothrombin time, anti-factor Xa activity, anti-factor IIa activity, and platelet aggregation. HBC reversed the enhancement of all tested parameters caused by HS demonstrating that cationic synthetic block copolymers may have a therapeutic value in various disorders involving overproduction of HS.

Graphical abstract: The neutralization of heparan sulfate by heparin-binding copolymer as a potential therapeutic target

Article information


Submitted
26 Nov 2018
Accepted
15 Jan 2019
First published
23 Jan 2019

This article is Open Access

RSC Adv., 2019,9, 3020-3029
Article type
Paper

The neutralization of heparan sulfate by heparin-binding copolymer as a potential therapeutic target

B. Kalaska, J. Miklosz, K. Kamiński, B. Musielak, S. Yusa, D. Pawlak, M. Nowakowska, K. Szczubiałka and A. Mogielnicki, RSC Adv., 2019, 9, 3020 DOI: 10.1039/C8RA09724K

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