i-Motif DNA: structure, stability and targeting with ligands

Area of Science:

• Biochemistry
• Molecular Biology
• Nanotechnology

Background:

• i-Motifs are pH-responsive, four-stranded DNA secondary structures formed in cytosine-rich sequences.
• Their stability is pH-dependent, with acidic conditions favoring formation via cytosine-cytosine(+) base pairs.
• Historically considered unstable at physiological pH, limiting biological applications.

Purpose of the Study:

• To review diverse i-motif structures and factors influencing their topology, stability, and dynamics.
• To discuss existing ligands that interact with i-motif DNA.
• To provide perspective on challenges in targeting i-motif structures for biological functions.

Main Methods:

• Literature review of i-motif structures, stability factors, and ligands.
• Analysis of sequence and environmental influences on i-motif topology.
• Examination of ligand interactions with i-motif DNA.

Main Results:

• i-Motif stability is not universally precluded at physiological pH; it is sequence and condition-dependent.
• Various i-motif structures exhibit different topologies and dynamics.
• Several ligands capable of interacting with i-motif DNA have been identified.

Conclusions:

• Advances in understanding i-motif stability expand their potential biological roles.
• Targeting i-motif DNA with ligands presents opportunities and challenges for research.
• Further investigation into i-motif ligands is crucial for exploring their biological functions.