Anticoagulant potential of regioselective derivatized cellulose

Regioselective derivatization was carried out introducing sulfate, phosphat e or quaternary ammonia groups in C2-, C3- and C6-position of the anhydrogl ycose unit of cellulose. The anticoagulant potential of these derivatives w as estimated with common clotting assays, such as thrombin time and partial thromboplastin time. It was found that a pronounced anticoagulant activity of cellulose derivatives could be achieved if the degree of substitution ( DS) with sulfate was above 1.0. The anticoagulant activity was maximal at a DS of about 1.5 and then decreased again. Further, it was detected that pa rticularly sulfation in C2-position resulted in a pronounced anticoagulant activity of cellulose derivatives. Development and application of assays sp ecific for thrombin and factor Xa indicated that the anticoagulant potentia l of these cellulose derivatives was mainly due to anti-thrombin activity. The comparison of cellulose sulfates and cellulose derivatized with phospha te and quaternary ammonium groups demonstrated that the negative charge and type of the substituent is an important prerequisite for the anticoagulant activity of cellulose derivatives. Indeed, derivatization with sulfate pro duced superior activity in comparison with phosphate. (C) 2001 Elsevier Sci ence Ltd. All rights reserved.