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Effect of oligodeoxynucleotide thrombin aptamer on thrombin inhibition by heparin cofactor II and antithrombin
Author(s) -
Holland Carrie A,
Henry Alexis T,
Whinna Herbert C,
Church Frank C
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)02131-1
Subject(s) - thrombin , heparin cofactor ii , aptamer , serpin , chemistry , antithrombin , heparin , dermatan sulfate , antithrombins , biochemistry , discovery and development of direct thrombin inhibitors , serine protease , glycosaminoglycan , protease , microbiology and biotechnology , heparan sulfate , enzyme , platelet , biology , immunology , gene
‘Thrombin aptamers’ are based on the 15‐nucleotide consensus sequence of d(GGTTGGTGTGGTTGG) that binds specifically to thrombin's anion‐binding exosite‐I. The effect of aptamer–thrombin interactions during inhibition by the serine protease inhibitor (serpin) heparin cofactor II (HCII) and antithrombin (AT) has not been described. Thrombin inhibition by HCII without glycosaminoglycan was decreased ∼two‐fold by the aptamer. In contrast, the aptamer dramatically reduced thrombin inhibition by >200‐fold and 30‐fold for HCII–heparin and HCII–dermatan sulfate, respectively. The aptamer had essentially no effect on thrombin inhibition by AT with or without heparin. 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.