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端粒G-四链体DNA是由端粒末端富含鸟嘌呤的DNA序列通过自身组装形成的一种特殊的二级结构。配体通过结合/稳定端粒G-四链体DNA可以抑制端粒酶延长端粒DNA,从而抑制了癌细胞赖以生存的端粒维持机制。本文运用Discovery Studio3.5软件中的Structure Based Pharmacophore(SBP)方法,以分子间端粒G-四链体DNA四聚体的结构为基础,构建了具有抗肿瘤功效的药效团模型。并通过分析测试集与药效团模型的匹配情况,对模型进行了验证。证明了该模型的正确性和可靠性,此药效团模型可用于天然产物数据库的高通量虚拟筛选。
Telomere G-quadruplex DNA is a special secondary structure formed by the assembly of its own end-terminal guanine-rich DNA sequences. Ligands can inhibit telomerase prolongation of telomeric DNA by binding / stabilizing telomeric G-quadruplex DNA, thereby inhibiting telomere maintenance of cancer cells. Based on the Structure Based Pharmacophore (SBP) method in Discovery Studio3.5 software, a pharmacophore model with anti-tumor efficacy was constructed based on the structure of intermolecular telomeric G-quadruplex DNA tetramers. The model was verified by analyzing the matching between test set and pharmacophore model. The correctness and reliability of the model are proved. The pharmacophore model can be used for high-throughput virtual screening of natural product databases.