pH-Dependent Switching of Base Pairs Using Artificial Nucleobases with Carboxyl Groups

Area of Science:

• Synthetic chemistry
• Nucleic acid chemistry
• Biochemistry

Background:

• Oligonucleotides are crucial for molecular biology and nanotechnology.
• Developing responsive nucleic acid structures is key for advanced molecular devices.
• Novel nucleobases can impart unique functionalities to oligonucleotides.

Purpose of the Study:

• To synthesize modified oligonucleotides incorporating benzoic acid or isophthalic acid residues as novel nucleobases.
• To investigate the pH-dependent recognition properties of these modified oligonucleotides.
• To explore the potential for pH-responsive base pair switching.

Main Methods:

• Synthesis of modified oligonucleotides with benzoic acid and isophthalic acid residues.
• UV thermal denaturation analysis to assess duplex stability.
• Evaluation of base recognition and binding at various pH conditions (5.0, 6.0, 7.0, 8.0).

Main Results:

• Modified oligonucleotides demonstrated pH-dependent recognition of natural nucleobases.
• An isophthalic acid residue on a d-threoninol backbone showed preferential binding to adenine at pH 5 and guanine at pH 7-8.
• This is the first reported instance of pH-responsive base pair switching in oligonucleotides without significant changes in duplex stability.

Conclusions:

• Benzoic acid and isophthalic acid residues can function as novel nucleobases in modified oligonucleotides.
• The observed pH-responsive base pair switching offers a new mechanism for molecular control.
• These findings pave the way for the development of advanced pH-responsive DNA-based molecular devices.