Real-Space Spectral Determination of Short Single-Stranded DNA Sequence Structures

化学 序列(生物学) 空格(标点符号) DNA 生物物理学 计算生物学 生物化学 哲学 语言学 生物
作者
Yu Han,Dong Li,Lifeng Zhu,Chunrui Hu,Hang Li,Yang Zhang,Chao Zhang,Yao Zhang,Zhen‐Chao Dong
出处
期刊:Journal of the American Chemical Society [American Chemical Society]
被引量:1
标识
DOI:10.1021/jacs.4c12393
摘要

Resolving the sequence and structure of flexible biomolecules such as DNA is crucial to understanding their biological mechanisms and functions. Traditional structural biology methods remain challenging for the analysis of small and disordered biomolecules, especially those that are difficult to label or crystallize. Recent development of single-molecule tip-enhanced Raman spectroscopy (TERS) offers a label-free approach to identifying nucleobases in a single DNA chain. However, a clear demonstration of sequencing both spatially and spectrally at single-base resolution is still elusive due to the challenges caused by weak Raman signals and the flexibility of DNA molecules. Here, we report a proof-of-principle demonstration to this end, spectrally resolving in real space individual nucleobases and their sequence structures within a short, single-stranded DNA molecule artificially designed. This breakthrough is achieved through the development of subnanometer-resolved low-temperature TERS methodology for such thermally unstable flexible biomolecules. Further TERS mapping over individual nucleobases provides additional structural information about the molecular configurations and even the locations of functional groups, offering a way to track modification types and binding sites in biomolecules.
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