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Simulation for fluorescence detection of O4-methylthymidine with definite photophysical characteristics
Chenyang Zhang1, Yu Zhao1, Menglu Cui1
1School of Physics and Electronics, Shandong Normal University, Jinan 250358, China.
Abstract:
DNA alkylation is caused by long-term exposure of cells to the environmental and endogenous alkylating agents, which can also lead to DNA mutations and therefore trigger some cancers. Since O4-methylthymidine (O4-meT), mismatched with guanine (G), is the most common but not easily repaired alkylated nucleoside, monitoring O4-meT can help to effectively reduce the occurrence of carcinogenesis. In this work, the modified G-analogues are selected as the fluorescence probe to monitor the existence of O4-meT according to its pairing characteristics. The photo-physical properties of considered G-analogues formed by ring expansion or addition of fluorophores were studied in detail. It is found that, compared with natural G, the absorption peaks of these fluorescence analogues are red-shifted (>55 nm) and the luminescence is enhanced by π-conjugation. Especially, the xG has a large Stokes shift (65 nm) with fluorescence insensitive to natural cytosine (C) and retains efficient emission after pairing, while it is sensitive to O4-meT and the quenching phenomenon occurs due to the excited state intermolecular charge transfer. Accordingly, the xG can be used as a fluorescent probe to identify the O4-meT in solution. In addition, the direct use of deoxyguanine fluorescent analogue for monitoring O4-meT was evaluated by the effects of ligating deoxyribose on absorption and fluorescence emission.
Insights
Monitoring O4-methylthymidine (O4-meT) is crucial for cancer prevention. Researchers developed a guanine (G) analogue fluorescent probe, xG, that detects O4-meT through fluorescence quenching, aiding in early carcinogenesis detection.
Area of Science:
- Molecular Biology
- Biochemistry
- Chemical Biology
Background:
- DNA alkylation from environmental and endogenous agents can cause mutations and cancer.
- O4-methylthymidine (O4-meT) is a common, poorly repaired alkylated nucleoside linked to carcinogenesis.
- Monitoring O4-meT levels is vital for reducing cancer occurrence.
Purpose of the Study:
- To develop a sensitive fluorescence probe for detecting O4-meT.
- To utilize modified guanine (G) analogues for O4-meT monitoring based on pairing characteristics.
- To investigate the photophysical properties of G-analogues for specific O4-meT detection.
Main Methods:
- Synthesis and characterization of modified G-analogues as fluorescence probes.
- Detailed study of photophysical properties, including absorption and luminescence.
- Evaluation of probe performance in solution, assessing sensitivity to O4-meT and natural nucleobases.
Main Results:
- Modified G-analogues exhibit red-shifted absorption (>55 nm) and enhanced luminescence due to π-conjugation.
- The xG analogue shows a large Stokes shift (65 nm), is insensitive to cytosine (C), and retains emission upon pairing.
- xG exhibits fluorescence quenching upon interaction with O4-meT, attributed to excited state intermolecular charge transfer.
Conclusions:
- The developed xG analogue serves as an effective fluorescent probe for identifying O4-meT in solution.
- This probe facilitates monitoring of O4-meT, a key factor in carcinogenesis.
- The study also explored the impact of deoxyribose ligation on the probe's optical properties for potential applications.
