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Heparin reversal by an oligoethylene glycol functionalized guanidinocalixarene

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. H...

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Autores principales: Huang, Qiaoxian, Zhao, Hong, Shui, Mingju, Guo, Dong-Sheng, Wang, Ruibing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162181/
https://www.ncbi.nlm.nih.gov/pubmed/34094229
http://dx.doi.org/10.1039/d0sc03922e
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author Huang, Qiaoxian
Zhao, Hong
Shui, Mingju
Guo, Dong-Sheng
Wang, Ruibing
author_facet Huang, Qiaoxian
Zhao, Hong
Shui, Mingju
Guo, Dong-Sheng
Wang, Ruibing
author_sort Huang, Qiaoxian
collection PubMed
description 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.
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spelling pubmed-81621812021-06-04 Heparin reversal by an oligoethylene glycol functionalized guanidinocalixarene Huang, Qiaoxian Zhao, Hong Shui, Mingju Guo, Dong-Sheng Wang, Ruibing Chem Sci Chemistry 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. The Royal Society of Chemistry 2020-08-28 /pmc/articles/PMC8162181/ /pubmed/34094229 http://dx.doi.org/10.1039/d0sc03922e Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Huang, Qiaoxian
Zhao, Hong
Shui, Mingju
Guo, Dong-Sheng
Wang, Ruibing
Heparin reversal by an oligoethylene glycol functionalized guanidinocalixarene
title Heparin reversal by an oligoethylene glycol functionalized guanidinocalixarene
title_full Heparin reversal by an oligoethylene glycol functionalized guanidinocalixarene
title_fullStr Heparin reversal by an oligoethylene glycol functionalized guanidinocalixarene
title_full_unstemmed Heparin reversal by an oligoethylene glycol functionalized guanidinocalixarene
title_short Heparin reversal by an oligoethylene glycol functionalized guanidinocalixarene
title_sort heparin reversal by an oligoethylene glycol functionalized guanidinocalixarene
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162181/
https://www.ncbi.nlm.nih.gov/pubmed/34094229
http://dx.doi.org/10.1039/d0sc03922e
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