Effect of oligodeoxynucleotide thrombin aptamer on thrombin inhibition by heparin cofactor II and antithrombin
Effect of oligodeoxynucleotide thrombin aptamer on thrombin inhibition by heparin cofactor II and antithrombin
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DOI：
10.1016/s0014-5793(00)02131-1
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发表时间：
2000-11-03
期刊：
影响因子：
3.5
通讯作者：
Church, FC
中科院分区：
文献类型：
--
作者：
Holland, CA;Henry, AT;Church, FC
“凝血酶适体”是基于d（GGTTGGTGTGGTTGG）的15个核苷酸的共有序列，其特异性结合凝血酶的阴离子结合外切位点-I。在丝氨酸蛋白酶抑制剂（丝氨酸蛋白酶抑制剂）、肝素辅因子II（HCII）和抗凝血酶（AT）的抑制作用期间，适体-凝血酶相互作用的影响尚未得到描述。不含糖胺聚糖的HCII对凝血酶的抑制被适体降低了约两倍。相反，对于HCII-肝素和HCII-硫酸皮肤素，适体分别将凝血酶抑制显著降低> 200倍和30倍。这些结果增加了我们对凝血酶适体活性的理解，用于潜在的临床应用，并且它们进一步证明了凝血酶外切位点-I在HCII-糖胺聚糖抑制期间的重要性。(C)2000年欧洲生物化学学会联合会。由Elsevier Science B. V.出版，版权所有。
'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.