Prof. Yi Lu, University of Illinois at Urbana-Champaign

New Metallo-DNAzymes: from Fundamental Insights into
Metal-binding Sites in Nucleic Acids to Practical Applications in Sensing, Imaging and Nanotechnology

One of the most important discoveries in the last decade is that DNA molecules are not only materials for genetic information storage, but also catalysts for a variety of biological reactions, and thus called DNAzymes. Since metal ions play essential roles in the structure and function of DNAzymes, the study and application of these new metalloenzymes has become a new frontier in chemical biology.1 While different classes of metalloproteins have been studied, including a comprehensive understanding of their sequence, structural, and functional features specific to each metal ions, similar information about metal-specific DNAzymes is not available. We have obtained new DNAzymes that bind transition metal ions with high affinity and selectivity through the use of a combinatorial biology tool called in vitro selection.2 The work makes it possible to obtain different classes of metallo-DNAzymes in the laboratory within a short period of time. It also offers a rare opportunity to compare and contrast structural and functional properties of metal-binding sites in proteins and in DNAzymes.3 Furthermore, by labelling the resulting DNAzymes with fluorophore/quencher pair4 or gold nanoparticles,5 we have converted those DNAzymes into highly sensitive and selective sensors for metal ions. A novel approach of using an inactive variant of DNAzymes to tune the detection range of the sensors is also demonstrated. Recently we have expanded the technology to sensing and imaging non-metal ions such as organic and bio-molecules using aptamers. The use of these functional nucleic acids in directed assembly of smart nanomaterials such as nanoparticles, quantum dots and nanotubes in responsive to multiple chemical stimuli, with controlled cooperativity under complex chemical and biological media,6 and capable of proof-reading and error-correction7 has also been achieved. Recent progress in these areas will be presented.

[1] Y. Lu, Chem. Euro. J. 8, 4588 (2002); Y. Lu and J. Liu, Curr. Opion. Biotech. 17, 580 (2006); Y. Lu and J. Liu, Acc. Chem. Res. 40, 315 (2007); [2] J. Li, et al., Nucleic Acids Res. 28, 481 (2000); [3] A. K. Brown, et al., Biochemistry, 42, 7152 (2003); H. Kim. J. Am. Chem. Soc. 129, 6896-6902 (2007); [4] J. Li, Y. Lu, J. Am. Chem. Soc. 122, 10466 (2000); J. Liu et al. Proc. Natl. Acad. Sci. USA 104, 2056 (2007); [5] J. Liu, Y. Lu, J. Am. Chem. Soc. 125, 6642 (2003); J.-H. Lee, Z. Wang and Y. Lu, J. Am. Chem. Soc. 130, 14217-14226 (2008); [6] J. Liu, Y. Lu, Adv. Mater. 1667 (2006); [7] J. Liu, D. P. Wernette, Y. Lu, Angew. Chem., Int. Ed. 44, 7290 (2005).

For more information contact Prof. Christoph Fahrni (404-385-1164).