Plant derived small molecules, which interact with and stabilize G-quadruplex DNA, act as inhibitors of telomere elongation and oncogene expression in humans. The inhibition of telomerase enzyme has immense potential since it is over expressed in most cancer cells. Interaction of palmatine, an antitumor alkaloid, to parallel G-quadruplex DNA, [d(TTGGGGT)]₄ and [d(TTAGGGT)]₄, has been investigated using Nuclear Magnetic Resonance (NMR), fluorescence and Circular Dichroism (CD) spectroscopy. Titrations were monitored by ¹H and ³¹P NMR spectra and solution structure of palmatine-[d(TTGGGGT)]₄ complex was obtained by restrained Molecular Dynamics (rMD) simulations using distance restraints from 2D NOESY spectra. Thermal stabilization of DNA was determined by CD, ¹H NMR and Differential Scanning Calorimetry (DSC). Binding of palmatine induces 98% enhancement of fluorescence accompanied by blue shift ∼8 nm. CD spectral bands of DNA show minor changes. Diffusion NMR studies confirm formation of a stable complex. Proton NMR signals of palmatine shift upfield upon binding and NOE cross peaks of H10, H3, H28, 5OCH₃ protons with T2, A3/G3, G6 and T7 residues reveal dual recognition sites in both G-quadruplex DNA sequences, resulting in thermal stabilization of G-quadruplex by ∼13–17 °C. Restrained molecular dynamics simulations using NOE distance restraints for 2:1 palmatine-[d(TTGGGGT)]₄ complex reveal end-stacking of palmatine at G6pT7 step and groove binding along T2pG3 step. Binding to [d(TTAGGGT)]₄ takes place at T2pA3pG4 and G6pT7 steps. Structural features of molecular recognition of two different G-quadruplex DNA sequences by palmatine have relevance in rational drug development for anti-cancer therapy.

植物衍生的小分子与G-四链体DNA相互作用并使其稳定，可作为人类端粒延长和癌基因表达的抑制剂。端粒酶的抑制作用具有巨大的潜力，因为它在大多数癌细胞中都过度表达。使用核磁共振（NMR），荧光和圆二色性（CD）光谱法研究了抗肿瘤生物碱棕榈碱与平行G-四链体DNA [d（TTGGGGT）] ₄和[d（TTAGGGT）] _4的相互作用。。通过¹ H和³¹ P NMR光谱和巴马汀-[d（TTGGGGT）] _4的溶液结构监测滴定通过使用2D NOESY光谱的距离约束，通过约束分子动力学（rMD）模拟获得复合物。通过CD，¹ H NMR和差示扫描量热法（DSC）确定DNA的热稳定性。棕榈碱的结合诱导了98％的荧光增强，并伴有〜8 nm的蓝移。DNA的CD谱带显示微小变化。扩散NMR研究证实形成了稳定的络合物。结合和H10，H3，H28、5OCH _3的NOE交叉峰使棕榈碱的质子NMR信号向高场移动具有T2，A3 / G3，G6和T7残基的质子在两个G-四链体DNA序列中均显示出双重识别位点，从而在约13-17°C的温度下使G-四链体具有热稳定性。使用NOE距离约束的2：1棕榈碱-[d（TTGGGGT）] _4配合物的受限分子动力学模拟显示，棕榈碱在G6pT7步骤的末端堆积和在T2pG3步骤的凹槽结合。与[d（TTAGGGT）] _4的绑定在T2pA3pG4和G6pT7步骤进行。棕榈碱对两种不同的G-四链体DNA序列的分子识别结构特征与合理的抗癌药物开发有关。