Synthesis Of PEGylated Heparin With Anticoagulant Activity By Thiol-ene Click Chemistry

Heparin is a natural polysaccharide substance in human body.With efficient anticoagulant activity,heparin plays an important role in the treatment of anticoagulant diseases.In our study,we described a novel,efficient and mild approach(reactions in aqueous solution)to functionalize heparin via its hydroxyl groups and then obtained an allyl glycidyl-heparin conjugate through a stable ether bond linkage by the method of freeze-drying,finally synthesized PEGylated heparin by thiol-ene click chemistry.Heparin's PEGylating we presented is a new modification method for heparin,which has not been reported before.Unfractionated heparin,after modification,retained the anticoagulant activity,and prolonged its half-life in the body.Theoretically,in this way,a defect of unfractionated heparin,such as the T1/2 is short and high occurring probability of adverse reactions,will be solved.The breakthrough of our study is,by using the method of freeze drying facilitate the opening of glycidyl ether ether key ring reaction for the first time;Finding a novel modified method,which coupled the M-PEG-SH to heparin by thiol-ene click chemistry;Provides a new PEGylated method,widen the application range of PEGylating technology,can be used to not only the drugs contained amino,but also contained sulfydryl and hydroxyl.Due to its biocompatible,biodegradable and long-acting anticoagulant activity,PEGylated heparin is expected to be widely used in drug release,postoperative prevent thrombus formation,and the preparation of anticoagulant biomaterials and long-acting preparations.