A new modified thrombin binding aptamer containing a 5'-5' inversion of polarity site.
A new modified thrombin binding aptamer containing a 5'-5' inversion of polarity site.
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一种新的修饰凝血酶结合适体，其中包含极性位点的5'-5'反转。
DOI：
10.1093/nar/gkl915
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发表时间：
2006
影响因子：
14.9
通讯作者：
Mayol L
中科院分区：
文献类型：
--
作者：
Martino L;Virno A;Randazzo A;Virgilio A;Esposito V;Giancola C;Bucci M;Cirino G;Mayol L
报道了一种新的修饰凝血酶结合适体（TBA）的溶液结构，其包含一个5′–5′极性反转位点，即d(3′GGT5′ - 5′TGGTGTGGTTGG3′)。已使用核磁共振（NMR）和圆二色谱（CD）光谱以及分子动力学和力学计算来表征其三维结构。这种修饰的寡核苷酸的特征是一种椅状结构，由两个G - 四联体组成，通过三个侧向的TT、TGT和TT环连接。d(3′GGT5′ - 5′TGGTGTGGTTGG3′)具有一种不寻常的折叠方式，即三条链相互平行，只有一条链方向相反。这导致两个四联体中G的排列为反 - 反 - 反 - 顺和顺 - 顺 - 顺 - 反。该修饰寡核苷酸的热稳定性比相应的未修饰TBA高4°C。d(3′GGT5′ - 5′TGGTGTGGTTGG3′)仍然显示出抗凝血活性，尽管相对于TBA有所降低。
The solution structure of a new modified thrombin binding aptamer (TBA) containing a 5′–5′ inversion of polarity site, namely d(3′GGT5′-5′TGGTGTGGTTGG3′), is reported. NMR and CD spectroscopy, as well as molecular dynamic and mechanic calculations, have been used to characterize the 3D structure. The modified oligonucleotide is characterized by a chair-like structure consisting of two G-tetrads connected by three edge-wise TT, TGT and TT loops. d(3′GGT5′-5′TGGTGTGGTTGG3′) is characterized by an unusual folding, being three strands parallel to each other and only one strand oriented in opposite manner. This led to an anti-anti-anti-syn and syn-syn-syn-anti arrangement of the Gs in the two tetrads. The thermal stability of the modified oligonucleotide is 4°C higher than the corresponding unmodified TBA. d(3′GGT5′-5′TGGTGTGGTTGG3′) continues to display an anticoagulant activity, even if decreased with respect to the TBA.