Pd-mediated Sonogashira, Heck, and Suzuki-Miyaura cross-coupling reactions have been applied widely to modify peptides and proteins, where diverse Pd reagents have been developed for the application in aqueous solutions.  Those reactions require the protein or peptide substrate bearing unnatural functional groups such as alkyne, aryl halides, and aryl boronic acids, which can be achieved through genetic code expansion or post-translational modifications.