Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, USA.
J Am Chem Soc. 2013 Jun 19;135(24):9213-9. doi: 10.1021/ja404737q. Epub 2013 Jun 6.
Natural products have served as a rich source for the discovery of new nucleic acid targeting molecules for more than half a century. However, our ability to design molecules that bind nucleic acid motifs in a sequence- and/or structure-selective manner is still in its infancy. Xylopyridine A, a naturally occurring molecule of unprecedented architecture, has been found to bind DNA by a unique mode of intercalation. Here we show that the structure proposed for xylopyridine A is not consistent with the characterization in the original isolation report and does not bind B-form DNA. Instead, we report that the originally proposed structure for xylopyridine A represents a new class of conformationally dynamic structure-selective quadruplex nucleic acid binder. The unique molecular conformation locks out nonspecific intercalative binding modes and provides a starting point for the design of a new class of structure-specific nucleic acid binder.
天然产物作为发现新的核酸靶向分子的丰富来源，已经有半个多世纪了。然而，我们设计能够以序列和/或结构选择性方式结合核酸基序的分子的能力仍处于起步阶段。木吡喃酮 A 是一种具有前所未有的结构的天然存在的分子，已被发现通过独特的嵌入模式结合 DNA。在这里，我们表明，木吡喃酮 A 的结构与原始分离报告中的特征不一致，并且不结合 B 型 DNA。相反，我们报告说，木吡喃酮 A 的原始结构代表了一类新的构象动态结构选择性四链体核酸结合物。独特的分子构象排除了非特异性嵌入结合模式，并为设计新的结构特异性核酸结合物提供了起点。
