Development of innovative synthesis and purification techniques for fluorescent and bifunctional substrates of self - labelling protein tags

The project of my PhD is positioned at the interface of organic chemistry, medicinal chemistry, and biochemistry and it comprises two main parts. The first part is dedicated to the development of innovative synthesis and purification methods to obtain fluorescent substrates designed for self-labelling protein tags (SNAP-tag, CLIP-tag and Halo­ tag). Furthermore, a key innovation of this work is the design of a bifunctional molecule capable of selectively cross-linking SNAP-tag and HaloTag proteins, overcoming the potential cross-reactivity between SNAP-tag and CLIP-tag. The second part of the project focuses on the synthesis of two chimeric compounds, as a proof of concept, that operates through a mechanism of action similar to that of PROTAC degraders but utilize a substrate of the suicide protein AGT instead of a conventional E3 ligase substrate, in order to target and degrade protein of interest for which no inhibitors are currently available ("undruggable targets").