Bioorthogonal derivatization of peptides and proteins
enables investigations
into their biological function and allows for exploitation of their
therapeutic potential, among other varied deliverables. Herein, we
describe a marine halogenating enzyme-assisted bioconjugation strategy
in which an N-terminal leader peptide guides bromination of a C-terminal
Trp residue in genetically encoded peptides and proteins, setting
up further Trp arylation by Suzuki–Miyaura reactions. The bromination
and subsequent cross-coupling reactions are residue-specific and regiospecific
for the indole-6 position, occur under mild aqueous conditions, and
do not require any modification of other Trp residues in the substrate
peptide and/or protein. Workflows described herein demonstrate the
applicability of halogenating enzymes in bioorthogonal conjugation
chemistry.