Genetically Encoded 1,2-Aminothiols Facilitate Rapid and Site-Specific Protein Labeling via a Bio-orthogonal Cyanobenzothiazole Condensation

The Chin lab described the genetic encoding of a 1,2-aminothiol chemical handle in bacterial cells. This was achieved through the incorporation of an unnatural lysine amino acid into a protein, using an evolved pyrrolysyl-tRNA synthetase. The 1,2-aminothiol was used for selective bioconjugation reactions in the presence of cysteine residues. Interestingly, the 1,2-aminothiol was linked to the lysine via an amide bond instead of a carbamate bond that is typically more readily accepted by the synthetase.