Development of a Smart Fluorescent Probe Specifically Interacting with C-Myc I-Motif

Area of Science:

• Biochemistry and Molecular Biology
• Chemical Biology
• Genetics

Background:

• I-motif structures in DNA are crucial for biological regulation and represent potential therapeutic targets.
• The c-myc gene promoter i-motif is implicated in various cellular processes.
• Developing selective probes for i-motif structures is essential for understanding their function and for drug discovery.

Purpose of the Study:

• To develop a novel fluorescent probe, G59, for the selective detection and binding of the c-myc gene promoter i-motif.
• To characterize the binding properties and sensitivity of the G59 probe.
• To evaluate G59's utility in screening for ligands that interact with the c-myc i-motif.

Main Methods:

• Synthesis of G59, a fluorescent probe combining a carbazole moiety for i-motif binding and naphthalimide fluorescent groups.
• Spectroscopic analysis to confirm selective fluorescence activation upon binding to the c-myc i-motif.
• Determination of the probe's sensitivity and stabilization effect on the i-motif structure.

Main Results:

• G59 exhibits strong and selective binding to the c-myc i-motif, differentiating it from other DNA structures.
• The probe demonstrates selective fluorescence activation, allowing for apparent visualization in solution.
• G59 shows high sensitivity with a low fluorescent detection limit of 154 nM.
• The probe effectively stabilizes the c-myc i-motif structure.

Conclusions:

• G59 is a novel, highly sensitive fluorescent probe for recognizing the c-myc i-motif.
• G59 facilitates label-free screening of selective c-myc i-motif binding ligands under neutral crowding conditions.
• This probe represents a significant advancement for studying i-motif structures and discovering related therapeutic agents.