Modifications of Amino Acids and Peptides via Radicals

Wessig P. Synthesis and modifications of amino acids and peptides via diradicals. In Renaud P, Sibi M, eds. Radicals in Organic Synthesis. Wiley, 2001. 

Peptides and proteins represent, apart from the nucleic acids, the most important class of compounds governing the basic biochemical principles in nature. During the last hundred years the synthesis of natural and unnatural amino acids as well as peptide synthesis has experienced a breathtaking development. The interest in this process has grown as the knowledge about the relationship between the structure of peptides and proteins and their physiological effects has increased. Nowadays the chemist may refer to a variety of synthetic methods to prepare enantiomerically enriched or pure a-amino acids (for an overview see [1]). Nevertheless, the need for amino acids with a very special substitution pattern often reveals the limits of the established methods. Consequently, the development of new synthetic routes to a-amino acids (and, naturally, also to 8-amino acids, which have enjoyed increased attention over the last years) is playing an important role in the current chemical research. This chapter reviews the application of a special part of radical chemistry in the synthesis and modification of amino acids and peptides, namely reactions that proceed via diradicals. 

Galactose oxidase, as well as the other non-blue oxidases, avoids the necessity of an external cofactor by creating an internal cofactor via modification of a residue of its own peptide chain. The amino acid residue which is modified in all cases is a tyrosine. While the amine oxidases produce TOPA quinone, galactose oxidase forms a thioether bond between the tyrosine and a cysteine residue. This modified tyrosine is the site which carries the free radical. 

---