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Issue 35, 2020
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Heparin reversal by an oligoethylene glycol functionalized guanidinocalixarene

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Abstract

Unfractionated heparin (UFH), a naturally occurring anionic polysaccharide, is widely used as an anticoagulant agent in clinical practice. When overdosed or used in sensitive patients, UFH may cause various risks and a UFH neutralizer needs to be administered immediately to reverse heparinization. However, the most common UFH neutralizer, protamine sulfate, often causes various adverse effects, some of which are life-threatening. Herein, we designed a highly biocompatible, oligoethylene glycol functionalized guanidinocalixarene (GC4AOEG) as an antidote against UFH. GC4AOEG and UFH exhibited a strong binding affinity, ensuring specific recognition and neutralization of UFH by GC4AOEG in vitro and in vivo. As a consequence, UFH-induced excessive bleeding was significantly alleviated by GC4AOEG in different mouse bleeding models. Additionally, no adverse effects were observed during these treatments in vivo. Taken together, GC4AOEG, as a strategically designed, biocompatible artificial receptor with strong recognition affinity towards UFH, may have significant clinical potential as an alternative UFH reversal agent.

Graphical abstract: Heparin reversal by an oligoethylene glycol functionalized guanidinocalixarene

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Supplementary files

Article information


Submitted
17 Jul 2020
Accepted
10 Aug 2020
First published
28 Aug 2020

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2020,11, 9623-9629
Article type
Edge Article

Heparin reversal by an oligoethylene glycol functionalized guanidinocalixarene

Q. Huang, H. Zhao, M. Shui, D. Guo and R. Wang, Chem. Sci., 2020, 11, 9623
DOI: 10.1039/D0SC03922E

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