THROMBIN-BINDING DNA APTAMER FORMS A UNIMOLECULAR QUADRUPLEX STRUCTURE IN SOLUTION
THROMBIN-BINDING DNA APTAMER FORMS A UNIMOLECULAR QUADRUPLEX STRUCTURE IN SOLUTION
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DOI：
10.1073/pnas.90.8.3745
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发表时间：
1993-04-15
影响因子：
11.1
通讯作者：
FEIGON, J
中科院分区：
文献类型：
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作者：
MACAYA, RF;SCHULTZE, P;FEIGON, J
我们已经使用二维H-1 NMR光谱研究凝血酶结合适体d（GGTTGGTGTGGTTGG）在溶液中的构象。这是一系列凝血酶结合DNA适体中的一种，其具有最近分离的共有15个碱基序列，并显示在体外抑制凝血酶催化的纤维蛋白凝块形成[Bock，L. C.的方法，格里芬湖C.的方法，莱瑟姆，J. A.，Vermaas，E. B。和Toole，J. J.（1992）Nature（伦敦）355，564-566]。寡核苷酸形成由两个G-四联体组成的单分子DNA四联体，所述两个G-四联体通过两个TT环和一个TGT环连接。一个潜在的T.T bp形成在两个TT环之间，穿过顶部G-四重峰的对角线。因此，共有序列中的所有不变碱基都是碱基配对的。该适体结构通过NMR确定，并说明该分子形成特定的折叠结构。这种结构的知识可用于进一步开发基于阿曲库肽的凝血酶抑制剂。
We have used two-dimensional H-1 NMR spectroscopy to study the conformation of the thrombin-binding aptamer d(GGTTGGTGTGGTTGG) in solution. This is one of a series of thrombin-binding DNA aptamers with a consensus 15-base sequence that was recently isolated and shown to inhibit thrombin-catalyzed fibrin clot formation in vitro [Bock, L. C., Griffin, L. C., Latham, J. A., Vermaas, E. B. & Toole, J. J. (1992) Nature (London) 355, 564-566]. The oligonucleotide forms a unimolecular DNA quadruplex consisting of two G-quartets connected by two TT loops and one TGT loop. A potential T.T bp is formed between the two TT loops across the diagonal of the top G-quartet. Thus, all of the invariant bases in the consensus sequence are base-paired. This aptamer structure was determined by NMR and illustrates that this molecule forms a specific folded structure. Knowledge of this structure may be used in the further development of oligonucleotide-based thrombin inhibitors.