Anticoagulant Heparin Mimetics via RAFT Polymerization.

Autor: Nahain AA, Ignjatovic V; Haematology Research , Murdoch Children's Research Institute , Parkville , Victoria 3052 , Australia.; Department of Paediatrics , The University of Melbourne , Parkville , Victoria 3010 , Australia., Monagle P; Haematology Research , Murdoch Children's Research Institute , Parkville , Victoria 3052 , Australia.; Department of Paediatrics , The University of Melbourne , Parkville , Victoria 3010 , Australia.; Department of Clinical Haematology , Royal Children's Hospital , Parkville , Victoria 3052 , Australia., Tsanaktsidis J; CSIRO Manufacturing , Research Way , Clayton , Victoria 3168 , Australia., Vamvounis G; College of Science and Engineering , James Cook University , Townsville , Queensland 4811 , Australia., Ferro V
Jazyk: angličtina
Zdroj: Biomacromolecules [Biomacromolecules] 2020 Feb 10; Vol. 21 (2), pp. 1009-1021. Date of Electronic Publication: 2019 Dec 30.
DOI: 10.1021/acs.biomac.9b01688
Abstrakt: Heparin, a sulfated polysaccharide derived from animal sources, is the most commonly used parenteral anticoagulant drug, but it suffers from significant safety and supply issues. Herein, we describe the preparation of heparin mimetic homo- and copolymers via the reversible addition-fragmentation chain transfer (RAFT) polymerization in water of commercially available (non-carbohydrate) sulfonated and carboxylated monomers. The anticoagulant activities of the polymers were assessed by activated partial thromboplastin time (APTT), thrombin clotting time (TCT), and for the more promising polymers, thrombin generation, antifactor Xa, and antifactor IIa assays. Sulfonated homopolymers studied herein displayed low cytotoxicity and significant anticoagulant activity in APTT, TCT, and thrombin generation assays. In addition, copolymers of sodium styrenesulfonate and acrylic acid [poly(SSS- co -AA)] displayed unprecedented antifactor IIa activity. This study demonstrates the potential of RAFT polymers as alternative anticoagulants for biomedical applications.
Databáze: MEDLINE