Synthesis of New Bodipy Hydrazide Fluorescent Probes for the Detection of Carbonylated Proteins Generated by Oxidative Stress

Oxidative stress is a cellular disorder implicated in various severe diseases and redox biology and represents an important field of research for the last decades. One of the major consequences of oxidative stress is the carbonylation of proteins, which is also a reliable marker to assess protein oxidative modifications. Accumulation of carbonylated proteins has been associated with aging and age‐related diseases and can ultimately causes cell death. Detection of these oxidative modifications is essential to understand and discover new treatments against oxidative stress. We describe the design and the synthetic pathway of new BODIPY fluorescent probes functionalized with hydrazide function for protein carbonyl labeling to improve existing methodologies such as 2D‐Oxi electrophoresis. Hydrazide BODIPY analogues show very good fluorescent properties such as NIR emission up to 633 nm and quantum yield up to 0.88. These new probes were validated for the detection and quantification of carbonylated proteins with 2D‐Oxi electrophoresis using mouse muscle protein extracts, as well as both flow cytometry and microscopy using oxidant stressed C2 C12 cells. Insert text for Table of Contents here. We report the design and the synthesis of new BODIPY possessing a hydrazide function (BODIPY−Hz), an emission in the near‐infra red area and high quantum yield. We show the use of these new BODIPY−Hz as fluorescent probes for carbonylated proteins labeling. We demonstrate that the new BODIPY−Hz are compatible with the 2D‐Oxi electrophoresis technology, and that it can be used directly for proteins labeling in cells monitored by fluorescence microscopy.