Sequence Isomerism in Uniform Polyphosphoesters Programmes Self-Assembly and Folding

Non-natural sequence-defined polymers have the potential to recapitulate the unique structures and functions of proteins. To achieve this goal requires not only high-efficiency synthesis platforms, but also an understanding of the relationship between sequence and folding/self-assembly. In a step towards that goal, we have here exploited the high-yielding solid phase phosphoramidite synthesis commonly used to make DNA, and generated two sequence-isomeric polymers which display sequence-programmed folding and self-assembly. These findings open up possibilities for more sophisticated sequence/structure relationships using the same synthetic platform.