Self-reporting affinity/activity based probes
The accurate identification of protein-ligand and protein-metabolite interactions remains one of the cornerstones of medicinal chemistry. The quest to identify a ligand’s target has spawned a myriad of techniques and approaches using a combination of synthetic, biological and medicinal chemistry. Although a number of approaches are available to identify protein-ligand interactions, there are issues with the types of interactions that they can detect, or the extra steps required to achieve the desired target identification.
We have designed a method, which we believe is a marked improvement on these two approaches and would provide a much more reliable and efficient approach for target identification. Our approach is based on results from our labs which have shown that a chloro-BODIPY unit is able to bind cysteine, in the process undergoes a significant wavelength shift. We have developed a bis-functionalised BODIPY unit which can be easily bound to a ligand of interest. The ligand provides the guidance and specificity for target recognition. Upon binding to its target, the protein should then be able to make a covalent interaction with the BODIPY unit, causing a wavelength shift. At the moment, we are working on applying this method on a number of known compounds as a proof of concept in collaboration with Astra-Zeneca, the University of Dundee and the Beatson Institute. The final aim of this programme is to develop a set of probes capable to providing real time readouts in proteomics research.
