Durand M, Thuong N T, Maurizot J C
Centre de Biophysique Moléculaire 1A, Orléans, France.
J Biol Chem. 1992 Dec 5;267(34):24394-9.
The interaction of netropsin, a minor groove binding drug, with T-A-T triple helix and A-T double helix was studied using circular dichroism spectroscopy and thermal denaturation. The triple helix was made by an oligonucleotide (dA)12-x-(dT)12-x-(dT)12, where x is a hexaethylene glycol chain bridged between the 3' phosphate of one strand and the 5' phosphate of the following strand. This oligonucleotide is able to fold back on itself to form a very stable triplex. Changing the conditions allows the same oligonucleotide in a duplex form with a (dT)12 dangling arm. Circular dichroism spectroscopy demonstrates that netropsin can bind to the triple helical structure. Spectral analysis shows that the bound drug exhibits a conformation and an environment similar in double-stranded and in triple-stranded structure. However, the binding constant to the triple-stranded structure is found smaller than the binding constant to the double-stranded one. Thermal denaturation experiments demonstrate that netropsin destabilizes the triplex whereas it stabilizes the duplex.
使用圆二色光谱法和热变性研究了小沟结合药物纺锤菌素与T-A-T三链螺旋和A-T双链螺旋的相互作用。三链螺旋由寡核苷酸（dA）12-x-（dT）12-x-（dT）12形成，其中x是连接一条链的3'磷酸基团和下一条链的5'磷酸基团的六甘醇链。这种寡核苷酸能够自身回折形成非常稳定的三链体。改变条件可使相同的寡核苷酸形成带有（dT）12悬垂臂的双链体形式。圆二色光谱法表明纺锤菌素可与三链螺旋结构结合。光谱分析表明，结合的药物在双链和三链结构中呈现相似的构象和环境。然而，发现其与三链结构的结合常数小于与双链结构的结合常数。热变性实验表明，纺锤菌素会使三链体不稳定，而使双链体稳定。
