Using SERS to Characterize Parallel DNA Structure

Characterizing parallel double-stranded DNA (dsDNA) is possible by using surface-enhanced Raman spectroscopy (SERS), according to a recent study published in Analytical Chemistry (1).

Parallel double-strand DNA refers to a structural arrangement of the DNA molecule where both strands run in the same direction, unlike the antiparallel arrangement found in the classic Watson-Crick model (2). In this configuration, both strands of the double helix have their 5' to 3' directionality oriented in the same direction (2). This conformation has been proposed in some non-canonical DNA structures and synthetic DNA molecules, although it contrasts with the predominant antiparallel orientation found in natural DNA. The implications of parallel double-strand DNA extend to its potential use in nanotechnology, particularly in DNA-based computing, molecular machines, and materials science (2). Researchers seek to understand the unique properties and behaviors of parallel double-strand DNA because the consensus is that it could unlock novel applications in biotechnology and nanoscience, driving innovation in various fields.

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However, the lack of robust characterization techniques has hindered its exploration. The research team, led by lead authors Xiaoxuan Xiang, Yang Tian, and Xinhua Guo, attempted to present a solution to this ongoing issue. Comprised of researchers from Jilin University and East China Normal University, the research team demonstrated a novel method that could characterize parallel dsDNA using SERS with gold nanoparticles modified by bromine and magnesium ions (Au BMNPs) as substrates (1).

Blue and red particles DNA helix glowing over dark blue background. | Image Credit: © vladimircaribb - stock.adobe.com

In their study, the research team showed the success of their new method could help improve molecular biology, diagnosis, therapy, and molecular assembly. The researchers showed that there was a series of intensive characteristic Raman bands specific to three types of parallel dsDNA (1). These structures were stabilized by various molecular interactions, including reverse Hoogsteen A+·A+ base pairs, hemiprotonated C+·C and G·G minor groove edge interactions, Hoogsteen A·A base pairs, and Hoogsteen T·A and C+·G base pairs (1).

The technique demonstrated in this study distinguished itself from traditional ones in two important ways. For one, the method used in the study was able to distinguish parallel dsDNA from antiparallel structures (1). The second key advantage is that it was able to identify the orientation of strands within the dsDNA (1). This level of precision in DNA analysis is significant because it had never been achieved before, according to the authors that led the study (1). As a result, their method could be valuable in fields that require precise DNA characterization.

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The implications of this research are broad. In molecular biology, it could lead to a deeper understanding of DNA-based processes, such as replication and transcription (1). In diagnostics, the ability to accurately differentiate between various DNA conformations could enhance the detection of genetic mutations and diseases. Moreover, in therapy, it could facilitate the design of more targeted and effective treatments (1).

As this technique gains traction, it is expected to catalyze further advancements in DNA analysis, which is critical for our understanding of biological functions.

References

(1) Zhang, Y.; Xiang, X.; Bao, Y.; et al. Characterization of Parallel-Stranded DNA Duplexes by Surface-Enhanced Raman Spectroscopy and Bromide-Modified Gold Nanoparticles. Anal. Chem. 2024, 96 (12), 4884–4890. DOI: 10.1021/acs.analchem.3c05356

(2) Szabat, M.; Kierzek, R. Parallel-Stranded DNA and RNA Duplexes - Structural Features and Potential Applications. FEBS J. 2017, 284 (23), 3986–3998. DOI: 10.1111/febs.14187