Abstract：
The interaction of small molecules with G quadruplexes is in focus due to its role in molecular recognition and therapeutic drug design. Stabilization of G-quadruplex structures in the promoter regions of oncogenes by small molecule binding has been demonstrated as a potential approach for cancer therapy.
In this study, electronic spectroscopy (ultraviolet-visible, fluorescence, circular dichroism), differential scanning calorimetry, and molecular modeling were employed to explore the interactions between the chemotherapy drug doxorubicin and a chlorin compound 5,10,15,20-tetraphenyl-[2,3]-[bis(carboxy)-methano]chlorin (H2TPC(DAC)), and the c-Myc 22-mer G quadruplex DNA.
Spectroscopic studies indicated external binding of the compounds with partial stacking at the end quartets. Calorimetric studies and temperature dependent circular dichroism data displayed increased melting temperatures of G quadruplex structure on binding with the compounds. Circular dichroism spectra indicated that the G quadruplex structure is intact upon ligand binding. Both the compounds showed binding affinities of the order of 106 M-1. Fluorescence lifetime studies revealed static quenching as major mechanism for fluorescence quenching. Polymerase chain reaction stop assay hinted that binding of both ligands under study could inhibit the amplification of the DNA sequence.
Results show that doxorubicin and H2TPC(DAC) bind to the 22-mer c-Myc quadruplex structure with good affinity and induce stability.
Doxorubicin and H2TPC(DAC) have demonstrated their affinity towards c-Myc G quadruplex DNA, stabilizing it and inhibiting expression and polymerization. The results can be of practical use in designing new analogs for the two compounds, which can become potent anti-cancer agents targeting the c-Myc GQ structure.
In this study, electronic spectroscopy (ultraviolet-visible, fluorescence, circular dichroism), differential scanning calorimetry, and molecular modeling were employed to explore the interactions between the chemotherapy drug doxorubicin and a chlorin compound 5,10,15,20-tetraphenyl-[2,3]-[bis(carboxy)-methano]chlorin (H2TPC(DAC)), and the c-Myc 22-mer G quadruplex DNA.
Spectroscopic studies indicated external binding of the compounds with partial stacking at the end quartets. Calorimetric studies and temperature dependent circular dichroism data displayed increased melting temperatures of G quadruplex structure on binding with the compounds. Circular dichroism spectra indicated that the G quadruplex structure is intact upon ligand binding. Both the compounds showed binding affinities of the order of 106 M-1. Fluorescence lifetime studies revealed static quenching as major mechanism for fluorescence quenching. Polymerase chain reaction stop assay hinted that binding of both ligands under study could inhibit the amplification of the DNA sequence.
Results show that doxorubicin and H2TPC(DAC) bind to the 22-mer c-Myc quadruplex structure with good affinity and induce stability.
Doxorubicin and H2TPC(DAC) have demonstrated their affinity towards c-Myc G quadruplex DNA, stabilizing it and inhibiting expression and polymerization. The results can be of practical use in designing new analogs for the two compounds, which can become potent anti-cancer agents targeting the c-Myc GQ structure.
摘要：
背景：小分子与G四链体的相互作用因其在分子识别和治疗药物设计中的作用而受到关注。通过小分子结合稳定癌基因启动子区域中的G-四链体结构已被证明是癌症治疗的潜在方法。
方法：在本研究中，电子光谱学（紫外可见，荧光，圆二色性)，差示扫描量热法,和分子模型被用来探索化疗药物阿霉素与氯化合物5,10,15,20-四苯基-[2,3]-[双（羧基）-甲基]氯（H2TPC（DAC））之间的相互作用，和c-Myc22-merG四链体DNA。
结果：光谱研究表明化合物的外部结合在末端四重奏部分堆积。量热研究和温度依赖性圆二色性数据显示，与化合物结合后，G四链体结构的熔融温度升高。圆二色光谱表明G四链体结构在配体结合时是完整的。两种化合物均显示106M-1量级的结合亲和力。荧光寿命研究表明，静态猝灭是荧光猝灭的主要机制。聚合酶链式反应停止测定暗示所研究的两种配体的结合可以抑制DNA序列的扩增。
结论:结果表明,阿霉素和H2TPC(DAC)以良好的亲和力与22-merc-Myc四链体结构结合并诱导稳定性。
结论：阿霉素和H2TPC（DAC）已经证明了它们对c-MycG四链体DNA的亲和力，稳定它并抑制表达和聚合。该结果可用于设计这两种化合物的新类似物，其可以成为靶向c-MycGQ结构的有效抗癌剂。
方法：在本研究中，电子光谱学（紫外可见，荧光，圆二色性)，差示扫描量热法,和分子模型被用来探索化疗药物阿霉素与氯化合物5,10,15,20-四苯基-[2,3]-[双（羧基）-甲基]氯（H2TPC（DAC））之间的相互作用，和c-Myc22-merG四链体DNA。
结果：光谱研究表明化合物的外部结合在末端四重奏部分堆积。量热研究和温度依赖性圆二色性数据显示，与化合物结合后，G四链体结构的熔融温度升高。圆二色光谱表明G四链体结构在配体结合时是完整的。两种化合物均显示106M-1量级的结合亲和力。荧光寿命研究表明，静态猝灭是荧光猝灭的主要机制。聚合酶链式反应停止测定暗示所研究的两种配体的结合可以抑制DNA序列的扩增。
结论:结果表明,阿霉素和H2TPC(DAC)以良好的亲和力与22-merc-Myc四链体结构结合并诱导稳定性。
结论：阿霉素和H2TPC（DAC）已经证明了它们对c-MycG四链体DNA的亲和力，稳定它并抑制表达和聚合。该结果可用于设计这两种化合物的新类似物，其可以成为靶向c-MycGQ结构的有效抗癌剂。
