Specific targeting of new borinic acids as hydrogen peroxide-responsive probes to proteins using HALO-Tag strategy
Résumé
Reactive Oxygen Species (ROS) are involved in numerous physiological processes. In particular, hydrogen peroxide (H2O2) at low concentration plays a critical role in the regulation of numerous biological activities as a signaling molecule. However, aberrant production or accumulation of highly diffusive H2O2 leads to oxidative stress conditions, which can cause biomolecules lesions associated with aging, cancer and several neurodegenerative diseases such as Alzheimer’s or Parkinson’s.[1] In order to detect hydrogen peroxide, many fluorogenic organic probes have been developed, relying on a boronate trigger. However, this design suffers from slow kinetics, preventing a special resolution of hydrogen peroxide imaging. To address this issue, our team has successfully developed borinic acid-based fluorogenic probes, which display kinetic constants 10,000-fold faster than their boronic acid analogs toward H2O2.[2] In this work, we wish to improve the design of the “Off-on” fluorogenic borinic acid-based sensors by adding a protein-specific targeting moiety, i.e. an HALO-Tag[3], to a naphthalic scaffold. The specific targeting of this new sensor will allow analysis of redox events at different subcellular levels.