Synthesis and Incorporation of a pH-Responsive Nucleoside Into DNA Sequences

Area of Science:

• Biochemistry
• Nanotechnology
• Synthetic Biology

Background:

• DNA's programmable thermodynamics and structural versatility make it ideal for molecular devices.
• Harnessing pH gradients is crucial for biological processes but challenging in DNA nanotechnology.
• Current pH-responsive DNA strategies have limitations in sequence constraints and physiological relevance.

Purpose of the Study:

• To develop a novel nucleoside with pH-sensitive base pairing near physiological pH.
• To enable dynamic control over DNA structures in response to pH changes.
• To create a versatile tool for advanced DNA nanotechnology applications.

Main Methods:

• Synthesis of an unnatural nucleoside with pH-sensitive base pairing.
• Characterization of the nucleoside's pairing properties and pH-dependent stability.
• Integration of the nucleoside into DNA sequences for programmable pH responsiveness.

Main Results:

• The unnatural nucleoside exhibits reversible switching of base pairing specificity near physiological pH.
• Duplex stability is modulated by pH, while canonical DNA sequences remain unaffected.
• Programmable DNA motifs can transition between duplex and single-stranded states based on pH.

Conclusions:

• The developed nucleoside offers a versatile platform for dynamic DNA nanotechnology.
• Potential applications include DNA nanomachines, biosensing, and targeted drug delivery.
• The nucleoside's physiological pKa may facilitate acid-base catalysis in DNAzymes and ribozymes.