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

FEBS Letters

Church, Frank C¹  Whinna, Herbert C¹  Henry, Alexis T¹  Holland, Carrie A¹ 

[1] Departments of Pathology and Laboratory Medicine, Pharmacology, and Medicine, and Center for Thrombosis and Hemostasis, The University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC 27599-7035, USA

关键词: Aptamer;    Serpin;    Thrombin;    Heparin cofactor II;    Antithrombin;    serpin;    serine protease inhibitor;    HCII;    heparin cofactor II;    AT;    antithrombin;    BSA;    bovine serum albumin;   

DOI  :  10.1016/S0014-5793(00)02131-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

‘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.

【 授权许可】

Unknown