Preparation Of Fatty Acids Modified Heparin Based On The Thio-ene Click Chemistry And Its Characterization

Heparin is a glycosaminoglycan that with complicated structure,it has good anticoagulant activity,and it has been used in the anticoagulation of surgery procedures and prevention and treatment of thromboembolic disorders for more than 50 years.As the further research about structure、activity of heparin,researchers find that heparin has other biological function,such as anti-inflammatory activity,anti-tumor activity,and it also can be used as scaffold materials in tissue engineering.Therefore,it has a good application prospect by modifying the structure of heparin in order to gain more valuable,more functional drugs.However,due to its complex structure,there are few studies about directly modifying heparin.Inspired by polypeptide drugs that modified with fatty acid,in this research,we first use fatty acids to modify the structure of heparin,for the preparation of new heparin anticoagulant drugs with long-acting potential.First,we synthesize 5 kinds of compounds that is thiolated lauric acid、thiolated myristic acid、thiolated palmitic acid、thiolated stearic acid and thiolated arachidic acid;then,synthesize and pick out 10 heparin-allyl conjugates after reaction between allyl glycidyl ether and heparin;finally,use thiolated fatty acids and heparin-allyl conjugates containing double bond for the click reaction through thiol-ene click chemistry,so as to realize the adipose modification of heparin structure,to obtain new heparin anticoagulant drugs.Through the chromogenic substrate method to detect the activity of modified heparin,we found there five samples have better activity than other samples,and their activity also increase relative to the heparin standard.The results showed that using fatty acid to modify heparin is feasible,and has further research value,it also has certain significance for the direct modification of heparin structure and the research of new heparin drugs.