Jump to main content
Jump to site search

Issue 6, 2019, Issue in Progress
Previous Article Next Article

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

Back to tab navigation

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

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material and it is not used for commercial purposes.

Reproduced material should be attributed as follows:

  • For reproduction of material from NJC:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
  • For reproduction of material from PCCP:
    [Original citation] - Published by the PCCP Owner Societies.
  • For reproduction of material from PPS:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
  • For reproduction of material from all other RSC journals:
    [Original citation] - Published by The Royal Society of Chemistry.

Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.


Social activity

Search articles by author

Spotlight

Advertisements