Detecting DNA-binding agents visually

A convenient colorimetric assay that could be used to screen drug candidates on the basis of how strongly they bind DNA has been developed by Chad A. Mirkin's group at Northwestern University (Angew. Chem. Int. Ed., published online Feb. 15, dx.doi.org/10.1002/anie.200504277). "This could dramatically speed up the identification of new anticancer agents," Mirkin says. The assay uses gold nanoparticles that have been functionalized with one of two complementary oligonucleotides. When the particles are mixed, the complementary strands hybridize, thereby forming particle aggregates that appear blue. Heating the mixture above a critical temperature reverses the process, and the particles dissociate with a concomitant blue-to-red color change (shown). If the two varieties of nanoparticles are mixed in the presence of a drug candidate that binds to duplex DNA, the duplexes formed between the particles will be more stable than ordinary duplexes, and it will require a higher temperature to dehybridize them and dissociate the aggregates. By visually monitoring the blue-to-red transition temperature, the researchers can determine how strongly or weakly a drug candidate binds to DNA to get an indication of its biological activity.