Are i-Motif Structures in DNA Compatible with Cytosine-Ag(I)-Cytosine Base Pairs?

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• DNA i-motifs are four-stranded DNA structures stabilized by hemiprotonated C:CH+ base pairs at acidic pH.
• These structures are of interest for nanotechnology and therapeutics.
• The stability and potential modification of i-motifs at neutral pH are actively researched.

Purpose of the Study:

• To investigate the feasibility of replacing protons in C:CH+ base pairs of DNA i-motif structures with silver ions (Ag+).
• To characterize the structural and stability changes upon silver ion incorporation into an i-motif/duplex junction (IDJ).
• To assess the compatibility of DNA i-motif structures with the formation of C-Ag+-C base pairs.

Main Methods:

• Proton-nuclear magnetic resonance (1H NMR) spectroscopy
• Luminescence spectroscopy
• Temperature-dependent UV spectroscopy
• Isothermal titration calorimetry (ITC)
• Dynamic light scattering (DLS)
• Circular dichroism (CD) spectroscopy

Main Results:

• Only the most accessible C:CH+ base pair in the investigated IDJ could be converted to a C-Ag+-C base pair.
• Incorporation of more than one silver ion per IDJ induced structural rearrangement into larger aggregated structures.
• The aggregated structures likely involve non-canonical silver-mediated base pairing.

Conclusions:

• The DNA i-motif structure is generally not compatible with the formation of contiguous C-Ag+-C base pairs.
• Silver ion incorporation is limited to specific, accessible sites within the i-motif.
• Findings contrast with earlier reports suggesting broader compatibility of i-motifs with silver ions.