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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2020
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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. |
format | Online Article Text |
id | pubmed-8162181 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
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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