Rational Design of Abasic Site-Containing DNA Triplexes To Bind Small Molecules with Low Nanomolar Dissociation Constants.

Jian Liu, Tingting Jiang, Jiemin Zhao, Mingchun Liu, Fangfang Chen, Lixin Lin, Huawei He, Hua Zuo, Cheng Zhi Huang, Chengde Mao

Analytical chemistry 2023 Jul 04

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De novo design of functional biomacromolecules is of great interest to a wide range of fundamental science and technological applications, including understanding life evolution and biomacromolecular structures, developing novel catalysts, inventing medicines, and exploring high-performance materials. However, it is an extremely challenging task and its success is very limited. It requires a deep understanding of the relationships among the primary sequences, the 3D structures, and the functions of biomacromolecules. Herein, we report a rational, de novo design of a DNA aptamer that can bind melamine with high specificity and high affinity (dissociation constant Kd = 4.4 nM). The aptamer is essentially a DNA triplex, but contains an abasic site, to which the melamine binds. The aptamer-ligand recognition involves hydrogen-bonding, π-π stacking, and electrostatic interactions. This strategy has been further tested by designing aptamers to bind to guanosine. It is conceivable that such a rational strategy, with further development, would provide a general framework for designing functional DNA molecules.

Citation

Jian Liu, Tingting Jiang, Jiemin Zhao, Mingchun Liu, Fangfang Chen, Lixin Lin, Huawei He, Hua Zuo, Cheng Zhi Huang, Chengde Mao. Rational Design of Abasic Site-Containing DNA Triplexes To Bind Small Molecules with Low Nanomolar Dissociation Constants. Analytical chemistry. 2023 Jul 04;95(26):9754-9760