Institut de Chimie Moléculaire de l'Université de Bourgogne, CNRS UMR5260, 9 Avenue Alain Savary, 21000 Dijon, France.
Biochimie. 2012 Feb;94(2):442-50. doi: 10.1016/j.biochi.2011.08.012. Epub 2011 Aug 25.
Three-way junction DNA (TWJ-DNA, also known as 3WJ-DNA) is an alternative secondary DNA structure comprised of three duplex-DNAs that converge towards a single point, termed the branch point. This point is characterized by unique geometrical properties that make its specific targeting by synthetic small-molecules possible. Such a targeting has already been demonstrated in the solid state but not thoroughly biophysically investigated in solution. Herein, a set of simple biophysical assays has been developed to identify TWJ-specific small-molecule ligands; these assays, inspired by the considerable body of work that has been reported to characterize the interactions between small-molecules and other higher-order DNA (notably quadruplex-DNA), have been calibrated with a known non-specific DNA binder (the porphyrin TMPyP4) and validated via the study of a small series of triazacyclononane (TACN) derivatives (metal-free or not) and the identification of a fairly-affinic and exquisitely TWJ-selective candidate (a TACN-quinoline construct named TACN-Q).
三链 DNA（TWJ-DNA，也称为 3WJ-DNA）是一种替代的二级 DNA 结构，由三个双螺旋 DNA 汇聚到一个称为分支点的单点组成。该点具有独特的几何特性，使其可以通过合成小分子进行特异性靶向。这种靶向已经在固态中得到了证明，但在溶液中尚未进行深入的生物物理研究。在此，开发了一系列简单的生物物理测定法来鉴定 TWJ 特异性小分子配体；这些测定法受大量已经报道的用于表征小分子与其他高级 DNA（特别是四链 DNA）之间相互作用的工作的启发，已经用已知的非特异性 DNA 结合剂（卟啉 TMPyP4）进行了校准，并通过研究一系列三氮杂环壬烷（TACN）衍生物（金属或非金属）以及鉴定相当亲和性和高度 TWJ 选择性的候选物（一种名为 TACN-Q 的 TACN-喹啉构建体）进行了验证。
