Interactions between DNA and small molecules can provide new options for the assembly of DNA nanostructures. Hanadi F. Sleiman of McGill University, Hanbin Mao of Kent State University, Chengde Mao of Purdue University, and coworkers show that melamine triggers the formation of polythymine duplexes (Nat. Mater. 2020, DOI: 10.1038/s41563-020-0728-2). On two of its three faces, melamine forms three hydrogen bonds with thymine. X-ray crystal structures reveal that the resulting complex of polythymine and melamine consists of two antiparallel polythymine strands wrapped around a column of melamine molecules. To show that interactions of polythymine with free melamine can control the formation of DNA nanostructures, the researchers made DNA tiles that folded such that they had a single-stranded 10-base polythymine overhang. When the researchers treated the tiles with 10 millimolar melamine solution, they assembled into 1- or 2-dimensional arrays, depending on the shapes of the individual tiles. The researchers can tune the stability of the structures by varying the polythymine length and the melamine concentration.