A "Three-in-One" Multifunctional Probe for Bcl-2/Mcl-1 Profiling and Visualizing in Situ

Area of Science:

• Biochemistry
• Molecular Biology
• Chemical Biology

Background:

• Bcl-2 family proteins, including Bcl-2 and Mcl-1, are key regulators of apoptosis.
• These proteins are significant therapeutic targets in cancer treatment.
• Current methods lack probes for simultaneous in situ profiling of both Bcl-2 and Mcl-1.

Purpose of the Study:

• To develop a multifunctional molecular probe for simultaneous detection and visualization of Bcl-2 and Mcl-1.
• To create a tool for in situ profiling, capturing, enriching, and bioimaging of Bcl-2 and Mcl-1.

Main Methods:

• A "three-in-one" molecular design strategy was employed.
• The probe (BnN3-OPD-Alk) integrates a Bcl-2/Mcl-1 binding ligand, a fluorescent reporter, and a photoreactive azido group.
• The probe's affinity and fluorescence properties were characterized.

Main Results:

• BnN3-OPD-Alk demonstrated sub-micromolar affinities for Bcl-2 and Mcl-1.
• The probe exhibits bright green self-fluorescence.
• Successful application in vitro and in cells for labeling, capturing, enriching, and bioimaging of Bcl-2 and Mcl-1.

Conclusions:

• A novel multifunctional probe enables simultaneous in situ profiling of Bcl-2 and Mcl-1.
• This strategy facilitates precise early diagnosis of diseases involving both proteins.
• The probe offers potential for effective targeted therapy in dual Bcl-2/Mcl-1-related cancers.