Anticoagulant Heparin Mimetics via RAFT Polymerization

Heparin, a sulfated polysaccharide derived from animal sources, is the most commonly used parenteral anticoagulant drug, but 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, anti-factor Xa and anti-factor 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 styrene sulfonate and acrylic acid [poly(SSS-co-AA)] displayed unprecedented anti-factor IIa activity. This study demonstrates the potential of RAFT polymers as alternative a...