Topological Study of the Conformational Interconversion Pathway and Molecular Folding

通过晶体学和理论研究，确定了千金藤素的结构特征及其抗过氧化和清除自由基的活性。利用我们开发的适用于药物和植物化学化合物的综合构象搜索程序，计算了红霉素A（EMA）、克拉霉素（CAM）和阿奇霉素（AZM）等大环内酯类抗生素的构象变化。根据所得结果，我们预测大环主链的α链（1-8位）比ω链（9-13位）具有更高的柔性。实际上，在与任何生物大分子的配位复合物中，这些大环内酯的三维结构的多样性在α链而不是在ω链上观察到。在本工作中，我们研究了这些大环内酯类化合物的溶液结构，基于NMR光谱。我们成功地量化了α链和ω链的柔性。

Structural features of cepharanthine on its antiperoxidation and radical scavenging activities were determined by the crystallographic and theoretical studies. Our obtained results indicated that the conformational flexibility of this macrocyclic alkaloid was informative to the activities.We computed the conformational variations of macrolide antibiotics, erythromycin A (EMA), clarithromycin (CAM), and azithromycin (AZM), using our developed program of the comprehensive conformational search adaptive to the medicinal and phytochemical compounds. According to the obtained results, we predicted that the α-chains (at 1-8 positions) of the macrocyclic backborns obviously have higher flexibility than their ω-chains (at 9-13 positions). Actually, diversity of three-dimensional structure of these macrolides were observed at α-chain rather than at ω-chain, in the ligand-site complex with any biomacromolecules. In the present work, we investigated the solution structures of these macrolides, based on the NMR spectroscopy. We successfully quantified the flexibility of α- and ω-chains.