Fig. 6. A proposed strategy to chemically control proteins through ligand-mediated functional group interconversion to dehydroamino acids. Activation of Ser/Thr or Cys using sulfur(vi)-fluoride exchange (SuFEx)56 or cyanamide chemistry52 yielding site-selective Dha or Dhb incorporation (within a binding pocket or on a protein surface) is depicted. The unsaturated amino acids could then be intercepted by neighboring residues, interacting proteins, nucleophilic metabolites such as glutathione, or exogenous nucleophiles causing a loss- or gain-of-function as desired.
