Site-Specific Protein Modification via Reductive Amination of Genetically Encoded Aldehyde

Aldehyde represents an extremely useful bio-orthogonal group in chemical biology and has promoted the generation of high-quality bioconjugates in therapeutics development. However, the installation of an aldehyde group on a protein and subsequent conjugation remains technically inadequate in the aspect of site choice, substrate availability, and linkage stability. Herein, we take efforts to advance the genetic incorporation of an aldehyde-containing noncanonical amino acid in <i>E. coli</i> and then show that reductive amination could be a useful reaction in introducing various amine-containing molecules, including peptides, into a specific site of proteins.