Journal
FEBS LETTERS
Volume 484, Issue 2, Pages 87-91Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0014-5793(00)02131-1
Keywords
aptamer; serpin; thrombin; heparin cofactor II; antithrombin
Funding
- NHLBI NIH HHS [HL32656, 1K08HL04063] Funding Source: Medline
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'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 similar to 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. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
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