Issue 35, 2020

Heparin reversal by an oligoethylene glycol functionalized guanidinocalixarene

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

Supplementary files

Article information

Article type
Edge Article
Submitted
17 7 2020
Accepted
10 8 2020
First published
28 8 2020
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2020,11, 9623-9629

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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