End-on PEGylation of heparin: Effect on anticoagulant activity and complexation with protamine

last updated: 2023-08-02
ProjectCARTI-LIKE :: publications list
TitleEnd-on PEGylation of heparin: Effect on anticoagulant activity and complexation with protamine
Publication TypePapers in Scientific Journals
Year of Publication2023
AuthorsAmaral S., Lozano-Fernández T., Sabin J., Gallego A., da Silva Morais A., Reis R. L., Gonzalez-Fernández A., Pashkuleva I., and Novoa-Carballal R.

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.  

JournalInternational Journal of Biological Macromolecules
Date Published2023-07-26
KeywordsAntithrombin, Glycosaminoglycan, isothermal calorimetry, oxime ligation, Protamine, Reducing end
Peer reviewedyes

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