ChemBioChem (COVER): A “three-in-one” multi-functional probe for Bcl-2/Mcl-1 profiling and visualizing in situ

Authors: Xiaodong Zhang, Dr. Ziqian Wang, Zongwei Guo, Dr. Ting Song, Nianzhe He, Junjie Zhu, Keke Cao, Prof. Zhichao Zhang

Graphical Abstract

Double vision: A “three-in-one” multifunctional probe was designed by integrating the Bcl-2/Mcl-1 binding ligand, a fluorescent reporter group and a photoreactive group into the same scaffold, and further applied for protein profiling and bioimaging of both Bcl-2 and Mcl-1 simultaneously in situ.

Abstract

Bcl-2 and Mcl-1, the two arms of the anti-apoptotic Bcl-2 family proteins, have been identified as key regulators of apoptosis and effective therapeutic targets of cancer. However, no small-molecular probe is capable of profiling and visualizing both Bcl-2 and Mcl-1 simultaneously in situ. Herein, we report a multifunctional molecular probe (BnN3-OPD-Alk) by a “three-in-one” molecular designing strategy, which integrated the Bcl-2/Mcl-1 binding ligand, fluorescent reporter group and photoreactive group azido into the same scaffold. BnN3-OPD-Alk exhibited sub-micromolar affinities to Bcl-2/Mcl-1 and bright green self-fluorescence. It was then successfully applied for Bcl-2/Mcl-1 labeling, capturing, enriching, and bioimaging both in vitro and in cells. This strategy could facilitate the precise early diagnosis and effective therapy of dual Bcl-2/Mcl-1-related diseases.

https://doi.org/10.1002/cbic.202000441