Programmable Assembly of Amphiphilic DNA through Controlled Cholesterol Stacking.

The excellent programmability and modifiability of DNA has enabled chemists to reproduce a series of specific molecular interactions in self-assembled synthetic systems. Among diverse modifications, cholesterol conjugation can turn DNA into an amphiphilic molecule (cholesterol-DNA), driving the formation of DNA assemblies through the cholesterol-endowed hydrophobic interaction. However, precise control of such an assembly process remains difficult because of the unbiased accumulation of cholesterol. Here, we report the serendipitous discovery of the favored tetramerization of cholesterol in cholesterol-DNA copolymers that carry the cholesterol modification at the blunt end of DNA. The discovery expands the repertoire of controllable molecular interactions by DNA and provides an effective way to precisely control the hydrophobic stacking of cholesterol for programmed cholesterol-DNA assembly.