A novel thrombin binding aptamer containing a G-LNA residue

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• 作者：Ada Virno ; Antonio R ; azzo ; Concetta Giancola ; Mariarosaria Bucci ; Giuseppe Cirino ; Luciano Mayol
• 关键词：DNA ; LNA ; Quadruplex ; TBA ; NMR ; Anticoagulant activity
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2007
• 出版时间：1 September 2007
• 年：2007
• 卷：15
• 期：17
• 页码：5710-5718
• 全文大小：786 K

文摘

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.