Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/85961
Título: | End-on PEGylation of heparin: Effect on anticoagulant activity and complexation with protamine |
Autor(es): | Amaral, S. Lozano-Fernández, T. Sabin, J. Gallego, A. da Silva Morais, Alain Reis, R. L. Gonzalez-Fernández, A. Pashkuleva, I. Novoa-Carballal, Ramon |
Palavras-chave: | Antithrombin Glycosaminoglycan isothermal calorimetry oxime ligation Protamine Reducing end |
Data: | Jul-2023 |
Editora: | Elsevier |
Revista: | International Journal of Biological Macromolecules |
Citação: | Amaral, S., Lozano-Fernández, T., Sabin, J., Gallego, A., da Silva Morais, A., Reis, R. L., … Novoa-Carballal, R. (2023, September). End-on PEGylation of heparin: Effect on anticoagulant activity and complexation with protamine. International Journal of Biological Macromolecules. Elsevier BV. http://doi.org/10.1016/j.ijbiomac.2023.125957 |
Resumo(s): | Heparin is the most common anticoagulant used in clinical practice but shows some downsides such as short half- life (for the high molecular weight heparin) and secondary effects. On the other hand, its low molecular weight analogue cannot be neutralized with protamine, and therefore cannot be used in some treatments. To address these issues, we conjugated polyethylene glycol (PEG) to heparin reducing end (end-on) via oxime ligation and studied the interactions of the conjugate (Hep-b-PEG) with antithrombin III (AT) and protamine. Isothermal titration calorimetry showed that Hep-b-PEG maintains the affinity to AT. Dynamic light scattering demonstrated that the Hep-b-PEG formed colloidal stable nanocomplexes with protamine instead of large multi-molecular aggregates, associated with heparin side effects. The in vitro (human plasma) and in vivo experiments (Sprague Dawley rats) evidenced an extended half-life and higher anticoagulant activity of the conjugate when compared to unmodified heparin.  |
Tipo: | Artigo |
Descrição: | Supplementary data to this article can be found online at https://doi.org/10.1016/j.ijbiomac.2023.125957. |
URI: | https://hdl.handle.net/1822/85961 |
DOI: | 10.1016/j.ijbiomac.2023.125957 |
ISSN: | 0141-8130 |
Versão da editora: | https://doi.org/10.1016/j.ijbiomac.2023.125957 |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | 3B’s - Artigos em revistas/Papers in scientific journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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20960-1-s20-s0141813023028520-main.pdf | 3,13 MB | Adobe PDF | Ver/Abrir |
Este trabalho está licenciado sob uma Licença Creative Commons