The binding of metal ions to DNA/RNA is known to play important roles in transcription, translation or other regulation of biological functions in response to both beneficial and deleterious metal ions. Despite the importance, the nature of coordination and metal-binding specificity is still not well understood. Furthermore, despite the presence of numerous metal ions in living cells, selective metal sensors are still limited. To overcome both limitations, we have used in vitro selection method to obtain from a large DNA library of up to 1015 different sequences a new class of DNAzymes that are specific to almost any metal ions of interests, including mono-, di- and trivalent metal ions, with high specificity.1 We have carried out both biochemical and biophysical studies of these DNAzymes in order to elucidate features responsible for the selective binding of metal ions by the DNAzymes. Because of the high selectivity, these DNAzymes have been converted into fluorescent, colorimetric, electrochemical sensors and magnetic resonance imaging agents for detection of metal ions with high sensitivity (down to 14 pM limit of detection) and selectivity (up to millions of fold of selectivity).3 These DNAzymes have been delivered into cells through conjugation with gold nanoparticles,4 lipofectamine5 or cationic peptides.6 Together with photo-caged DNAzymes,5,6 these methods allow detection and imaging of a wide variety of metal ions in living cells with high spatial and temporal resolution. 1. a) J. Liu et al., Proc. Natl. Acad. Sci. USA 104, 2056–2061 (2007); b) Y. Xiang and Y. Lu, Inorg. Chem. 53, 1925–1942 (2014). 2. a) H.-K. Kim et al. Nature Chem. Biol. 3, 763-768 (2007); b) D. Mazumdar, et al. J. Am. Chem. Soc. 131, 5506-5515 (2009); c) T. Lan and Y. Lu, in Interplay between Metal Ions and Nucleic Acids", Metal Ions in Life Sciences, Vol. 10, A. Sigel, H. Sigel, R. K. O. Sigel, eds.; Springer Netherlands; pp. 217-248 (2012). 3. J. Liu, Z. Cao, Y. Lu, Chem. Rev. 109, 1948–1998 (2009). 4. P. Wu, et al. J. Am. Chem. Soc. 135, 5254-5257 (2013). 5. K. Hwang, et al. Angew. Chem. Inter. Ed. 53, 13798-13802 (2014). 6. S.-F. Torabi, et al. Proc. Natl. Acad. Sci. 112, 5903-5908 (2015).

In vitro selection and characterization of metal-specific DNAzymes and their applications in imaging metal ions in living cells

251st National Meeting (2016)

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