Parallel G-duplex and C-duplex DNA with Uninterrupted Spines of AgI-Mediated Base Pairs

TL;DR

This study demonstrates the formation of parallel G-duplex and C-duplex DNA structures mediated by silver ions, revealing new possibilities for DNA nanotechnology through metal-mediated base pairing.

Contribution

It introduces the first evidence of parallel G-Ag(I)-G and C-Ag(I)-C base pairs forming stable, linear DNA structures, expanding the understanding of metal-mediated DNA architectures.

Findings

Parallel G-Ag(I)-G duplexes up to 20 base pairs formed.

C-Ag(I)-C duplexes also form in parallel orientation.

G-Ag(I)-G duplexes are more rigid than B-DNA.

Abstract

Hydrogen bonding between nucleobases produces diverse DNA structural motifs, including canonical duplexes, guanine (G) quadruplexes and cytosine (C) i-motifs. Incorporating metal-mediated base pairs into nucleic acid structures can introduce new functionalities and enhanced stabilities. Here we demonstrate, using mass spectrometry (MS), ion mobility spectrometry (IMS) and fluorescence resonance energy transfer (FRET), that parallel-stranded structures consisting of up to 20 G-Ag(I)-G contiguous base pairs are formed when natural DNA sequences are mixed with silver cations in aqueous solution. FRET indicates that duplexes formed by poly(cytosine) strands with 20 contiguous C-Ag(I)-C base pairs are also parallel. Silver-mediated G-duplexes form preferentially over G-quadruplexes, and the ability of Ag+ to convert G-quadruplexes into silver-paired duplexes may provide a new route to manipulating these biologically relevant structures. IMS indicates that G-duplexes are linear and more rigid than B-DNA. DFT calculations were used to propose structures compatible with the IMS experiments. Such inexpensive, defect-free and soluble DNA-based nanowires open new directions in the design of novel metal-mediated DNA nanotechnology.