School of Biological Sciences, University of Southampton, Southampton, SO17 1BJ, United Kingdom.
Department of Chemistry, University of Oxford, Oxford, OX1 3TA, United Kingdom.
Biophys Chem. 2020 Jan;256:106270. doi: 10.1016/j.bpc.2019.106270. Epub 2019 Oct 21.
DNA strands can be designed to assemble into stable three-dimensional structures, based on Watson-Crick base pairing rules. The simplest of these is the DNA tetrahedron that is composed of four oligonucleotides. We have re-designed the sequence of a DNA tetrahedron so that it contains a single (AATT) binding site for the minor groove binding ligand Hoechst 33258. We examined the stability of this structure by placing fluorescent groups within each of its edges and have shown that all the edges melt at the same temperature in the absence of the ligand. The minor groove ligand still binds to its recognition sequence within the tetrahedron and increases the melting temperature of the folded complex. This ligand-induced stabilisation is propagated into the adjacent helical arms and the tetrahedron melts as a single entity in a cooperative fashion.
DNA 链可以根据 Watson-Crick 碱基配对规则设计成稳定的三维结构。最简单的结构是由四个寡核苷酸组成的 DNA 四面体。我们重新设计了 DNA 四面体的序列,使其包含一个用于小沟结合配体 Hoechst 33258 的单一(AATT)结合位点。我们通过在四面体的每个边缘放置荧光基团来检查该结构的稳定性,并表明在没有配体的情况下,所有边缘在相同温度下熔化。小沟配体仍与其四面体中的识别序列结合,并增加折叠复合物的熔点。这种配体诱导的稳定性会传递到相邻的螺旋臂上,四面体以协同方式作为一个整体熔化。