Project information
Traceless Affinity Probes for Targeted Alteration of Proteoforms (TAP-TAP)

Post-translational modifications (PTMs) diversify the ~70’000 different proteins synthesized by the human body
into millions of proteoforms. Dysregulation of PTMs is associated with many diseases, including
neurodegeneration or cancers but the molecular details of these associations are often poorly understood.
PTMs are traditionally controlled and studied by enzyme-based methods, which however fail if the responsible
enzymes are not known or highly promiscuous.
TAP-TAP offers a chemical (non-enzymatic) solution to controlling tyrosine sulfation—a difficult-to-study PTM
primarily found on extracellular proteins. The project will develop ‘ligand-directed’ reagents that selectively bind
to a protein target and install/remove a sulfate group via proximity-driven chemistry.
TAP-TAP brings new chemical probes for manipulating PTMs beyond current capabilities. The general concept
represents a chemical solution to a long-standing challenge in biology intractable with traditional methods.