Active conformation of a tumor promoter, teleocidin. A molecular dynamics study.
Active conformation of a tumor promoter, teleocidin. A molecular dynamics study.
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肿瘤促进剂 teleocidin 的活性构象。
DOI：
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发表时间：
1992
影响因子：
7.3
通讯作者：
Akiko Itai
中科院分区：
文献类型：
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作者：
Takatoshi Kawai;Tazuko Ichinose;Yasuyuki Endo;Koichi Shudo;Akiko Itai
阿替米丁是有效的肿瘤促进剂，具有九元内酰胺结构。Teleocidin及其小分子活性同系物（吲哚内酰胺）已知存在于至少两种构象状态（扭曲和沙发形式）之间的平衡中。对4种吲哚内酰胺类化合物进行了分子动力学（MD）计算，以考察其环的优选构象与生物活性之间的关系。结果表明，促肿瘤活性与10种可能构象中沙发型的存在比例密切相关。这意味着沙发形式是活性环构象，这是相容的与先前的结果独立地从teleocidin和佛波酯的叠加。每个吲哚内酰胺的构象的预测比例与NMR光谱分析所观察到的结果吻合得很好。高温分子动力学方法被证明是非常有用的预测这些环状化合物的优选结构，其中的整体稳定性的强烈影响的构象上的环上的取代基。
Telecidins are potent tumor promoters, having a nine-membered lactam structure. Teleocidins and their small-molecular-sized active congeners (indolactams) are known to exist in an equilibrium between at least two conformational states, the twist and the sofa form. Molecular dynamics (MD) calculations were performed on four indolactams, in order to examine the relationships between preferred ring conformations and the biological activities. It was shown that the tumor-promoting activities are closely related with the existence ratio of the sofa form among 10 possible conformations. This implies that the sofa form is the active ring conformation, which is compatible with the previous result obtained independently from the superposition of teleocidin and phorbol ester. The predicted ratios of conformers for each indolactam were in good agreement with those observed by NMR spectral analysis. The high-temperature MD method proved to be very useful for predicting the preferred structures of these cyclic compounds, in which the overall stabilities are strongly influenced by the conformations of substituent groups on the ring.