Holland C A, Henry A T, Whinna H C, Church F C
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.
FEBS Lett. 2000 Nov 3;484(2):87-91. doi: 10.1016/s0014-5793(00)02131-1.
'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 approximately 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.
“凝血酶适配体”基于d(GGTTGGTGTGGTTGG)的15个核苷酸共有序列，该序列可特异性结合凝血酶的阴离子结合外位点I。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）在抑制过程中适配体与凝血酶相互作用的影响尚未见报道。在没有糖胺聚糖的情况下，HCII对凝血酶的抑制作用被适配体降低了约两倍。相比之下，适配体分别使HCII-肝素和HCII-硫酸皮肤素对凝血酶的抑制作用显著降低了200倍和30倍。适配体对有或没有肝素的AT抑制凝血酶的作用基本没有影响。这些结果增进了我们对凝血酶适配体活性在潜在临床应用方面的理解，并且进一步证明了在HCII-糖胺聚糖抑制过程中凝血酶外位点I的重要性。
