A Genetically Encoded Norbornene Amino Acid for the Mild and Selective Modification of Proteins in a Copper‐Free Click Reaction

Abstract

Built in for clicks: A specially evolved pyrrolysyl-tRNA synthetase from Methanosarcina mazei was used to incorporate a norbornene amino acid into proteins in E. coli. This unit can be site-selectively modified under mild physiological conditions using a [3+2] cycloaddition reaction with nitrile imines (see scheme).