Selective chemical protein modification

Chemical modification of proteins is an important tool for probing natural systems, creating therapeutic conjugates and generating novel protein constructs. Site-selective reactions require exquisite control over both chemo-and regioselectivity, under ambient, aqueous conditions. There are now various methods for achieving selective modification of both natural and unnatural amino acids-each with merits and limitations-providing a 'toolkit' that until 20 years ago was largely limited to reactions at nucleophilic cysteine and lysine residues. If applied in a biologically benign manner, this chemistry could form the basis of true Synthetic Biology.