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J Am Chem Soc. 2013 Jul 31;135(30):11283-8. doi: 10.1021/ja404402b. Epub 2013 Jul 18.

Intercalators as molecular chaperones in DNA self-assembly.

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Department of Chemistry and Center for Self-Assembled Chemical Structures (CSACS), McGill University, 801 Sherbrooke Street West, Montreal, QC, H3A 0B8, Canada.


DNA intercalation has found many diagnostic and therapeutic applications. Here, we propose the use of simple DNA intercalators, such as ethidium bromide, as tools to facilitate the error-free self-assembly of DNA nanostructures. We show that ethidium bromide can influence DNA self-assembly, decrease the formation of oligomeric side products, and cause libraries of multiple equilibrating structures to converge into a single product. Using a variety of 2D- and 3D-DNA systems, we demonstrate that intercalators present a powerful alternative for the adjustment of strand-end alignment, favor the formation of fully duplexed "closed" structures, and create an environment where the smallest, most stable structure is formed. A new 3D-DNA motif, the ninja star, was self-assembled in quantitative yield with this method. Moreover, ethidium bromide can be readily removed using isoamyl alcohol extractions combined with intercalator-specific spin columns, thereby yielding the desired ready-to-use DNA structure.

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