The availability and reliability of strategies for molecular biosensing over a finely adjustable dynamic range is essential to enhance the understanding and control of vital biological process. To expand the versatili...The availability and reliability of strategies for molecular biosensing over a finely adjustable dynamic range is essential to enhance the understanding and control of vital biological process. To expand the versatility and utility of nucleic acid- related enzymes, we demonstrated a rational approach to acquiring tunable, pH-dependent deoxyribozymes （DNAzymes） with catalytic activities and response sensitivities that can be tuned through a simple change in solution pH. To do this, we capitalized upon the pH dependence of Hoogsteen interactions and designed i-motif- and triplex-based DNAzymes that can be finely regulated with high precision over a physiologically relevant pH interval. The modified DNAzymes are dependent upon pH for efficient cleavage of substrates, and their catalytic performance can be tuned by regulating the sequence of inserted i-motif/triplex structures. The principle of tunable, pH-dependent DNAzymes provides the opportunity to engineer pH-controlled DNA-machinery devices with unprecedented sensitivity to pH changes. For example, we constructed a DNA-walker device, the stepping rate of which could be adjusted by simply modulating solution pH within an interval of 5.6 to 7.4, as well as a DNA tetrahedron that can be opened at pH 6.4 and kept closed at pH 7.4. The potential of this approach is not limited to serve as pH-dependent devices, but rather may be combined with other elements to expand their practical usefulness.展开更多
基金The authors thank the National Basic Research Pro- gram of China （973 Program） （Nos. 2012CB720600, 2012CB720603, and 2012CB720604）, the National Natural Science Foundation of China （Nos. 21432008 and 81373256）.
文摘The availability and reliability of strategies for molecular biosensing over a finely adjustable dynamic range is essential to enhance the understanding and control of vital biological process. To expand the versatility and utility of nucleic acid- related enzymes, we demonstrated a rational approach to acquiring tunable, pH-dependent deoxyribozymes （DNAzymes） with catalytic activities and response sensitivities that can be tuned through a simple change in solution pH. To do this, we capitalized upon the pH dependence of Hoogsteen interactions and designed i-motif- and triplex-based DNAzymes that can be finely regulated with high precision over a physiologically relevant pH interval. The modified DNAzymes are dependent upon pH for efficient cleavage of substrates, and their catalytic performance can be tuned by regulating the sequence of inserted i-motif/triplex structures. The principle of tunable, pH-dependent DNAzymes provides the opportunity to engineer pH-controlled DNA-machinery devices with unprecedented sensitivity to pH changes. For example, we constructed a DNA-walker device, the stepping rate of which could be adjusted by simply modulating solution pH within an interval of 5.6 to 7.4, as well as a DNA tetrahedron that can be opened at pH 6.4 and kept closed at pH 7.4. The potential of this approach is not limited to serve as pH-dependent devices, but rather may be combined with other elements to expand their practical usefulness.
