UW-Madison researchers have developed an improved and simpler method for rapidly attaching azide (N3) groups to proteins in solution. Whereas the reaction described in P220072 required an oxidative reagent, the inventors have discovered that direct protein azidylation requires only copper(I), azide, and protein, and the reaction appears to specifically modify Histidine residues. The inventors have tested at least four salts of Cu(I) with success, have tested Cu(I) bound to two different ligands, and confirmed that Cu(II) doesn’t work, and they’ve successfully tested two sources for azide (the salt sodium azide (NaN3), or the azide donor azidotrimethylsilane (TMSN3)). The inventors have tested several different buffers and have determined that the reaction works in both organic and aqueous solvents.