Chiral Interaction Is a Decisive Factor To Replace d-DNA with l-DNA Aptamers.

Area of Science:

• Biochemistry
• Molecular Biology
• Biotechnology

Background:

• Nucleic acid aptamers are crucial in biosensing and medical diagnostics.
• Their application is limited by susceptibility to nucleases, reducing biostability.
• Improving aptamer biostability is essential for broader biological use.

Purpose of the Study:

• To develop a simple strategy for enhancing aptamer biostability.
• To investigate the use of left-handed DNA (l-DNA) instead of standard DNA (d-DNA) in aptamers.
• To assess the efficacy of l-DNA aptamers against various targets.

Main Methods:

• Directly replacing d-DNA in reported aptamers with l-DNA.
• Testing the resulting l-DNA aptamers against small molecule and biomacromolecule targets.
• Evaluating nuclease resistance and target recognition capabilities.

Main Results:

• l-DNA aptamers demonstrated significantly improved biostability due to resistance to nuclease digestion.
• The strategy was effective for nonchiral small molecules and chirality-independent chiral targets (e.g., ATP).
• Effectiveness was limited for chirality-dependent targets and biomacromolecules where DNA backbone chirality is involved in recognition.

Conclusions:

• Replacing d-DNA with l-DNA is a straightforward method to create highly biostable aptamers.
• This approach is particularly promising for applications requiring robust aptamers against specific targets.
• Further research may be needed for targets where DNA chirality is critical for binding.