HTG-四链体对甲基氮杂杯[6]吡啶的构象调控

Conformational Regulation Effect on Methylazacalix[6]pyridine by HT G-Quadruplex

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。

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 macr℃yclic compounds. Herein,we regulated the conformation of methylazacalix[6]pyridine（ MACP6） in solution by using 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.^1 H NMR and molecular d℃king revealed MACP6 preferably bound 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 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. This study introduced a new functional molecule into conformational regulation of heteracalixaromatics in solution.