Bioorthogonal Modification of Proteins Using Genetically Encoded Non-Natural Amino Acids

Chemical modification of proteins with bioorthogonal reaction and site-selectivity has been increasingly recognized for exquisite control over homogeneity and geometry, allowing more complex and various applications of proteins. The development of novel bioorthogonal reactions and their adaptation to protein chemistry in the form of genetically encoded non-natural amino acids are fueling widespread use of the so-called ‘bioorthogonal protein conjugation’. Site-specific incorporation of a non-natural amino acid technique precisely delivers a bioorthogonal group to any defined site in response to an expanded genetic code where a selective bond-forming reaction equips proteins with novel functionalities in a chemically well-defined and homogeneous manner.