Virno Ada, Randazzo Antonio, Giancola Concetta, Bucci Mariarosaria, Cirino Giuseppe, Mayol Luciano
Dipartimento di Chimica delle Sostanze Naturali, Università degli Studi di Napoli Federico II, via D Montesano 49, Napoli, Italy.
Bioorg Med Chem. 2007 Sep 1;15(17):5710-8. doi: 10.1016/j.bmc.2007.06.008. Epub 2007 Jun 8.
In this work, we report the solution structure, thermodynamic studies, and the pharmacological properties of a new modified thrombin binding aptamer (TBA) containing a G-LNA residue, namely d(5'-GGTTGGTGTGGTTGg-3'), where upper case and lower case letters represent DNA and LNA residues, respectively. NMR and CD spectroscopy, as well as molecular dynamics and mechanic calculations, has been used to characterize the three-dimensional 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(5'-GGTTGGTGTGGTTGg-3') is characterized by the same folding of TBA, being two strands parallel to each other and two strands oriented in opposite manner. This led to a syn-anti-syn-anti and anti-syn-anti-syn arrangements of the Gs in the two tetrads. d(5'-GGTTGGTGTGGTTGg-3') possesses an anticoagulant activity, even if decreased with respect to the TBA.
在本研究中，我们报道了一种新的含有G-LNA残基的修饰凝血酶结合适配体（TBA），即d(5'-GGTTGGTGTGGTTGg-3')的溶液结构、热力学研究及药理学性质，其中大写和小写字母分别代表DNA和LNA残基。已使用核磁共振和圆二色光谱以及分子动力学和力学计算来表征其三维结构。该修饰的寡核苷酸的特征在于具有由通过三个边缘相连的TT、TGT和TT环连接的两个G-四联体组成的椅状结构。d(5'-GGTTGGTGTGGTTGg-3')具有与TBA相同的折叠方式，即两条链彼此平行，另外两条链方向相反。这导致两个四联体中G的顺-反-顺-反和反-顺-反-顺排列。d(5'-GGTTGGTGTGGTTGg-3')具有抗凝活性，尽管相对于TBA其活性有所降低。
