Proteins can be detected using ensembles of DNA G-quadruplexes functionalized with a medley of fluorophores
Stimulated by how the mammalian nose works, scientists have recently begun to develop sensors based on arrays of supramolecular receptors that generate a measurable signature output to identify molecules. Measuring proteins in such a way could provide an accurate method for diagnosing diseases that are characterized by protein imbalance.
Now David Margulies and Andrew Hamilton from Yale University have developed1 a recognition system based on DNA that can identify proteins in samples as small as a single microlitre drop. The sensors are based on G-quadruplexes — structures made up of four strands of guanine-rich DNA that self-assemble into a square arrangement. Each of the four strands can be functionalized with a fluorophore. If two different fluorophores are used then the four strands can assemble into six different possible structures, creating an ensemble of different G-quadruplexes with a distinct fluorescence emission.
Non-specific interactions between a protein and the various G-quadruplex structures of an ensemble result in measurable changes to its fluorescence signature. Using an ensemble of G-quadruplexes functionalized with three fluorophores — pyrene, tamra and fluoroscein — Margulies and Hamilton showed that five proteins, including the related avidin and streptavidin, could be detected and distinguished by monitoring changes in fluorescence.
References
Margulies, D. & Hamilton, A.D. Protein recognition by an ensemble of fluorescent DNA G-quadruplexes. Angew. Chem. Int. Ed. 10.1002/anie.200804887 (2009)
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Armstrong, G. A nose for proteins. Nature Chem (2009). https://doi.org/10.1038/nchem.134
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DOI: https://doi.org/10.1038/nchem.134