Effect of oligodeoxynucleotide thrombin aptamer on thrombin inhibition by heparin cofactor II and antithrombin

'Thrombin aptamers' are based on the 15-nucleotide consensus sequence of d( GGTTGGTGTGGTTGG) that binds specifically to thrombin's anion-binding exosit e-I. The effect of aptamer-thrombin interactions during inhibition by the s erine protease inhibitor (serpin) heparin cofactor II (HCII) and antithromb in (AT) has not been described. Thrombin inhibition by HCII without glycosa minoglycan was decreased similar to two-fold by the aptamer, In contrast, t he aptamer dramatically reduced thrombin inhibition by > 200-fold and 30-fo ld for HCII-heparin and HCII-dermatan sulfate, respectively. The aptamer ha d essentially no effect on thrombin inhibition by AT with or without hepari n, These results add to our understanding of thrombin aptamer activity for potential clinical application, and they further demonstrate the importance of thrombin exosite-I during inhibition by HCII-glycosaminoglycans. (C) 20 00 Federation of European Biochemical Societies. Published by Elsevier Scie nce B.V. All rights reserved.