Work

Locked Nucleic Acid Stabilized Liquid Crystalline Phases

Year: 2025
Type: article
Abstract: Liquid crystalline (LC) phases formed by gapped DNA (GDNA) constructs, where two rigid duplexes are connected with a flexible single stranded linker, offer a versatile platform to investigate interactions between DNA molecules. Base pairs containing a locked nucleic acid (LNA-DNA or LNA-LNA pairs) are generally more stable compared to DNA-DNA pairs due to enhanced hydrogen bonding and/or attractive base stacking interactions. In concentrated solutions of GDNA constructs, the stability of terminal base pairs and the base stacking interactions between neighboring duplexes are critical for the formation of a bilayer smectic phase. By using temperature-resolved synchrotron small-angle X-ray scattering (SAXS) measurements, we quantified the impact of single LNA modification of terminal base pairs on the thermal stability of smectic LC phases. We observe that LNA-DNA terminal AT base pairing (A+T) increases the stability of the bilayer smectic phase by ∼9-18 °C relative to DNA-DNA pairing at the same duplex concentrations. While relatively large, this increase is still significantly less than the up to ∼30 °C increase observed when AT DNA-DNA pairs are replaced by GC pairs, suggesting the stacking interactions between A+T LNA-DNA base pairs are significantly weaker than those between unmodified GC base pairs. Our study illustrates the sensitivity of LC ordering in dense DNA solutions to a single nucleotide modification and demonstrates that LNA modifications can provide a new mechanism for tuning the stability of nucleic acid-based materials.
Source: Langmuir
Language: English
Open Access status: green
Award: G269764420
OpenAlex ID: W4416674720
FWCI: 0.162
Cites: 26
Cited by: 1
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