Detection of unusual DNA structures with nanoparticles

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Abstract
The generic global structure of the DNA double helix is well known, but at the base pair level there are a multitude of deviations from the `ideal'. These deviations can result in sequence-directed curvature of DNA over a few base pairs. We have used luminescent mineral nanoparticles of CdS in optical assays to detect these curved DNAs. The nanoparticles, originally developed by the materials science community as `quantum dots,' are approximately 20 - 100 angstroms in diameter, similar to proteins, and their photoluminescence is sensitive to the presence and nature of adsorbates. In this paper, we have investigated higher-order structures of nucleic acids that are correlated with human disease: triplet repeats of the single-stranded oligonucleotides 5'-(CCG)n-3' and 5'-(CGG)n-3'. These sequences fold into structures that have not been determined, but give characteristic spectra in circular dichroism spectroscopy. Under salt conditions where 5'- (CCG)7-3' and 5'-(CGG)7-3' fold into these higher-order structures, our nanoparticles bind them well but do not bind to normal double-helical DNA. This result may form the basis for future assays of higher-order DNA structures.

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