Although 20 natural amino acids served as the building blocks of proteins contain several functional groups including carboxylic acids, amides, thiols, thiol ethers, alcohols, basic amines, and alkyl and aryl groups, they are still unable to carry out all of the natural functions. In order to improve the precision and diversity of protein to perform the biological processes, organisms have provided a variety of posttranslational modifications including phosphorylation, methylation, acetylation, and hydroxylation, even evolved novel translational machinery to incorporate either selenocysteine or pyrrolysine. Inspired by biological system, many biological or chemical methods have been developed to alter or insert new building blocks into protein, which enable protein to perform relevant functions or have some special properties, even create a new kind of enzyme. Here, we give a brief overview of the strategies for protein modification and the latest progress in this field.
Contents
1 Introduction
2 Chemical approaches
2.1 Chemical modification of proteins
2.2 Chemical synthesis
2.3 Semisynthesis
3 Biosynthetic approaches in vitro
4 Biosynthetic approaches in vivo
4.1 Incorporating unnatural amino acids into proteins using auxotrophic bacterial strains
4.2 Expanding genetic code
5 Functionalization and applications
5.1 'Click’ chemistry
5.2 Alkyne and azide functionalization
5.3 Keto and aldehyde functionalization
5.4 Alkene functionalization
5.5 Other functional unnatural amino acids
6 Conclusion and prospects