Förtsch I, Birch-Hirschfeld E, Schütz H, Zimmer C
Abteilung Molekulare Biologie, Friedrich-Schiller-Universität Jena, Germany.
J Biomol Struct Dyn. 1996 Dec;14(3):317-29. doi: 10.1080/07391102.1996.10508127.
The interaction of the nonintercalating bisquaternary ammonium heterocyclic drugs SN-18071 and SN-6999 with a DNA triple helix has been studied using thermal denaturation and CD spectroscopy. Our data show, that both minor groove binders can bind to the triple helix of poly(dA).2poly(dT) under comparable ionic conditions, but they influence the stability of the triplex relative to the duplex structure of poly(dA).poly(dT) in a different manner. SN-18071, a ligand devoid of forming hydrogen bonds, can promote triplex formation and thermally stabilizes it up to 500 mM Na+ concentration. SN-6999 destabilizes the triplex to duplex equibilirium whereas it stabilizes the duplex. The binding constant of SN-18071 is found to be greater than that to the duplex. The stabilizing effect of SN-18071 is explained by electrostatic interactions of three ligand molecules with the three grooves of the triple stranded structure. From the experiments it is concluded that SN-6999 binds to the triplex minor groove thereby destabilizing the triplex similar as previously reported for netropsin.
已使用热变性和圆二色光谱法研究了非嵌入性双季铵杂环药物SN - 18071和SN - 6999与DNA三链螺旋的相互作用。我们的数据表明，在可比的离子条件下，这两种小沟结合剂都能与聚（dA）·2聚（dT）的三链螺旋结合，但它们以不同方式影响三链体相对于聚（dA）·聚（dT）双链结构的稳定性。SN - 18071是一种不形成氢键的配体，在高达500 mM Na⁺浓度下可促进三链体形成并使其热稳定。SN - 6999使三链体与双链体的平衡不稳定，而它使双链体稳定。发现SN - 18071与三链体的结合常数大于与双链体的结合常数。SN - 18071的稳定作用是由三个配体分子与三链结构的三个沟的静电相互作用来解释的。从实验得出结论，SN - 6999与三链体小沟结合，从而使三链体不稳定，这与先前报道的纺锤菌素情况类似。
