Recently, the research group led by Yaoqi Zhou at Shenzhen Bay Laboratory published a research paper titled "Design and synthesis of large Stokes shift DNA dyes with reduced genotoxicity" in the journal Biochemical and Biophysical Research Communications. The paper reports the discovery of a new type of DNA fluorescent dye characterized by a large Stokes shift and low genotoxicity. This breakthrough was primarily led by Dr. Jian Zhan and Dr. Xiaofeng Rao, aiming to meet the growing demand for highly sensitive and safe nucleic acid dyes.

Fluorescence imaging technology, as a low-cost, highly sensitive, and minimal photodamage to biological samples tool for preclinical biomedical research, has been widely used in various fields and is crucial for life science research and clinical diagnosis. Developing high-performance fluorescent dyes with a large Stokes shift is particularly important because a large Stokes shift (Δλ>120 nm) can reduce spectral crosstalk between excitation and emission, improve the signal-to-background ratio, and thus facilitate high-resolution fluorescence imaging. Despite extensive research over the past few decades, only a few small molecule DNA fluorescent dyes with large Stokes shifts have been discovered. Most DNA probes on the market have a small Stokes shift, and some dyes with a larger Stokes shift have high genotoxicity, limiting their widespread application.

Benzimidazole compounds, which can strongly interact non-covalently with DNA rich in adenine-thymine (A-T) sequences, have attracted attention in the biotechnology field. The new small molecule DNA dyes (Benthio Green-1 to Bentho Green-5) developed by the team are based on an innovative thiazole-benzimidazole framework, with a Stokes shift range of 135 to 143 nm, and also exhibit low genotoxicity. These new dye molecules were synthesized through an efficient, modular, and scalable method, laying the foundation for the widespread application of these dyes. In particular, Bentho Green-4 has a DNA staining capacity 50% higher than the commonly used Hoechst 33342, with a detection limit as low as 1 ng (compared to 8 ng for Hoechst 33342), and it showed non-mutagenicity in the L5178Y TK gene mutation assay. The research team stated that this has important application prospects in the fields of biochemistry and fluorescence probe technology, especially in occasions that require high-resolution fluorescence imaging and low genotoxicity.

The success of this research not only fills the gap for DNA probes with a large Stokes shift and low genotoxicity but also brings a new perspective to the development of DNA-specific fluorescent dyes. It demonstrates the team's innovative capabilities in the field of fluorescence probe technology and provides safer and more efficient tools for future biomedical research. The research team believes that this study will receive widespread attention in the fields of chemical biology and fluorescence probe technology.

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Fig 1. Design and synthesis of large Stokes shift DNA dyes with reduced genotoxicity.