Rydzewski J M, Leupin W, Chazin W
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Nucleic Acids Res. 1996 Apr 1;24(7):1287-93. doi: 10.1093/nar/24.7.1287.
A complex between d(GGGAAAAACGG).d(CCGTTTTTCCC) and the minor groove binding drug SN-6999 has been studied by 1H nuclear magnetic resonance spectroscopy. The drug is found to bind in the d(A)5 tract, but with interactions extending one residue in the 3'-direction along each strand. Doubling of resonances in the complex indicates slow to intermediate exchange between two binding modes. An orientational preference (7:3) is found, the first such example in an SN-6999 complex. Furthermore, the upper limit of the lifetime for the major species is longer than was found for SN-6999 with other DNA duplexes. The preferred orientation of SN-6999 has the pyridinium ring near the 5'-end of the (+) strand; the minor binding mode has the reverse orientation. The orientational preference and slower exchange rate relative to other SN-6999 complexes is attributed to increased stabilization from van der Waals interactions due to better shape complementarity between the DNA duplex and ligand. The comparison of these results with studies of SN-6999 complexed to other DNA duplexes reveals the sensitivity of the binding properties to the delicate interplay between the molecular structure of the ligand and the specific characteristics of the DNA minor groove.
通过氢核磁共振光谱研究了d(GGGAAAAACGG).d(CCGTTTTTCCC)与小沟结合药物SN - 6999形成的复合物。发现该药物结合在d(A)5区域，但相互作用沿每条链在3'方向延伸一个残基。复合物中共振信号加倍表明两种结合模式之间的交换速率从慢到中等。发现了一种取向偏好（7:3），这是SN - 6999复合物中的首个此类例子。此外，主要物种寿命的上限比SN - 6999与其他DNA双链体的情况更长。SN - 6999的偏好取向是吡啶鎓环靠近(+)链的5'端；次要结合模式具有相反的取向。相对于其他SN - 6999复合物，其取向偏好和较慢的交换速率归因于DNA双链体与配体之间更好的形状互补性导致范德华相互作用增强，从而使稳定性增加。将这些结果与SN - 6999与其他DNA双链体形成复合物的研究进行比较，揭示了结合特性对配体分子结构与DNA小沟特定特征之间微妙相互作用的敏感性。
