A tridentate "click" nucleoside for metal-mediated base pairing

Area of Science:

• Chemical Biology
• Nucleic Acid Chemistry
• Supramolecular Chemistry

Background:

• Development of artificial nucleosides for novel DNA structures.
• Exploration of metal-mediated base pairing for DNA stabilization.
• Advancements in click chemistry for nucleoside synthesis.

Purpose of the Study:

• To establish a silver(I)-mediated base pair within a B-DNA double helix.
• To investigate the effect of this metal-mediated base pair on DNA thermal stability.
• To explore the synthesis and applicability of new click nucleosides.

Main Methods:

• Synthesis of artificial nucleosides incorporating a 6-(1H-1,2,3-triazol-4-yl)-2,2'-bipyridine ligand.
• Formation of DNA duplexes with canonical, hetero, and homo base pairs.
• Thermal stability assays (e.g., melting temperature measurements).
• UV and Circular Dichroism (CD) spectroscopy for metal coordination analysis.

Main Results:

• A stable silver(I)-mediated base pair was formed between an artificial nucleoside and an imidazole nucleoside in a B-DNA helix.
• The silver(I)-mediated base pair ([3+1] coordination) increased DNA duplex thermal stability by approximately 5 °C.
• UV and CD spectroscopy confirmed silver(I) ion coordination to the DNA.
• A homo base pair of the artificial nucleoside did not form a stabilizing metal-mediated pair due to unfavorable coordination geometry ([3+3]).

Conclusions:

• A novel silver(I)-mediated base pair enhances the stability of DNA duplexes.
• This work demonstrates the utility of click nucleosides in creating metal-stabilized DNA structures.
• The findings expand the scope of artificial nucleosides and metal-mediated base pairing in nucleic acid engineering.