中文关键词:甲基氮杂杯[n]吡啶 G-四链体 手性诱导 构象调控 英文关键词:Methylazacalix[n]pyridine, G-quadruplex, Chiral induction, Conformational regulation 基金项目:国家自然科学基金(21573126, 21675162, 21472197, 21778058, 31200576, 21472197, 21303225, 31200576)及北京自然科学基金(7172248)

作者	单位	E-mail
李敬晨	曲阜师范大学 化学与化工学院	lijingchen92@163.com
管爱娇	中国科学院化学研究所 分子动态与稳态结构国家重点实验室
向俊锋	中国科学院大学
张恩选	凯莱英医药集团 天津市药物绿色合成技术企业重点实验室
李骞	中国科学院化学研究所 分子动态与稳态结构国家重点实验室
齐伟	曲阜师范大学 化学与化工学院
孙红霞	中国科学院化学研究所 分子动态与稳态结构国家重点实验室
唐亚林	中国科学院化学研究所 分子动态与稳态结构国家重点实验室	tangyl@iccas.ac.cn

摘要点击次数:1705 全文下载次数:0 中文摘要: 甲基氮杂杯[n]吡啶 (MACPn) 是一类柔性、多构象的新型杂杯杂芳烃化合物,溶液状态中对其构象的调控与分离一直是此类化合物研究的难点之一。我们将DNA G-四链体作为功能分子,调控甲基氮杂杯[6]吡啶 (MACP6) 在溶液态的构象,结果表明,HT序列在K₊条件下所形成的混合结构的G-四链体可以诱导MACP6的手性构象,而在Na₊条件下所形成的反平行结构不具备此功能。一维核磁共振氢谱,分子对接与碱基突变进一步揭示了HT G-四链体与MACP6以边沿loop为位点的构型匹配作用模式,loop区增长,有利于HT G-四链体对MACP6的调控作用。本研究再次拓展了G-四链体作为氮杂杯吡啶构象调控功能分子的应用。 英文摘要: Methylazacalix[n]pyridine (MACPn) is a new type of flexible, multi-conformational heteracalixaromatics. However, the regulation and separation of its conformation in solution has always been one of the difficulties in macrocyclic compounds. Herein, we regulated the conformation of methylazacalix[6]pyridine (MACP6) in solution by DNA G-quadruplex. Human telomeric sequence HT could form 3+1 hybrid or antiparallel structure in K₊ or Na₊ solution, respectively. We found that the hybrid structure of HT G-quadruplex could induce the chiral conformation of MACP6, whereas, the antiparallel structure could not. The ₁H-NMR and molecular docking revealed MACP6 preferably bond to the T18-T19-A20 edge loop of HT G-quadruplex by spatially matching mode. Therefore, the topology of HT G-quadruplex played a vital role in conformational regulation of MACP6. The effect of edge loop on the chiral induction of MACP6 was further evidenced by base mutation, which was conducted by changing the number of T bases in loop region. The chiral induction ability on chiral induction of MACP6 related to length of the loop: (TTATTT) ≈ (TTATT) ≈ (TTAT) > (TA) > (TTA). All of these demonstrated that increasing the length of the edge loop was beneficial to the conformational regulation of MACP6 by HT G-quadruplex, but no remarkable effect could be observed with excessive loop length. In summary, we have shown the conformational regulation of MACP6 by telomeric HT G-quadruplex and further revealed the binding mode, which introduced a new functional molecule into conformational regulation of heteracalixaromatics in solution. 查看全文查看/发表评论下载PDF阅读器 相关附件：附件1附件2版权转让声明书 -->