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

Abstract

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 K d = 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.

Self-assembled methodologies for the construction of DNA nanostructures and biological applications

“…Based on this, a novel design strategy of the DNA aptamer with high specificity and high affinity for melamine was reported, which may be further promoted for the development of functional DNA molecules. 60 In addition to mediating and influencing the Watson–Crick base pairing, some other small molecule components could also be utilized for regulating the self-assembly process using their structural properties; Mao proposed a pH-responsive mechanism by using ethylenediamine (EN) as a regulator to overcome the electrostatic repulsion in the DNA assembly process. 61 In this case, the use of EN was demonstrated as a general method for DNA construction.…”

Polarity-Specific and Pyrimidine-over-Purine Adaptive Triplex DNA Recognition by a Near-Infrared Fluorogenic Molecular Rotor

“…In addition, with their structural uniqueness, triplex DNAs have been widely explored in molecular switches, − nanodevices, − DNA crystals, catalysis, and directing chemical reactions . Practically, triplex DNAs have also been employed as sensor elements for the recognition and analysis of nucleic acids, − proteins, ,, toxic metal ions, , pH, and bioactive small molecules. ,− Furthermore, versatile chemical modifications with DNAs diversify the triplex structures with promise even in cell manipulation.…”