Heparin-like anticoagulant polypeptides with tunable activity: Synthesis, characterization, anticoagulative properties and clot solubilities in vitro

Highlights: • A series of Heparin-like Anticoagulant Polypeptides with tunable activity is synthesized. • The anticoagulant activity can be controlled simply by adjusting the molecular weight or the ratio of the monomers. • With SO₃-, the Heparin-like Polypeptides can inhibit Factor IIa and Xa, prolong APTT, and show an anticoagulant effect. • The Heparin-like polypeptides hardly cause decrease and activations of platelets, excepting to reduce the incidence of HIT. Due to the uncontrollable anticoagulant activity and limited source, Heparin, which is commonly used in clinical anticoagulation therapies, faces the risk of spontaneous bleeding and thrombocytopenia. Herein, a series of anionic poly(amino acid) s poly (l-Serine-ran-L-Glutamic acid-ran-L-Cysteine-SO₃) (PSEC-SO₃) were prepared by the controlled Ring Opening Polymerization (ROP) of N-Carboxyanhydrides (NCAs). The anticoagulant activities of PSEC-SO₃ can be regulated by simply adjusting the feeding ratio of monomers. In vitro tests show that these polypeptides can effectively prolong the Activated Partical Thromboplastin Time (APTT) and inhibit Factor IIa and Factor Xa, but has no significant effect on Prothrombin Time (PT) and Thrombin Time (TT), which indicates that PSEC-SO₃ mainly act on the intrinsic pathway. In summary, the activity-tunable heparin-like polypeptides are expected to have good application prospects in the anticoagulant field.