Bio-orthogonal Imine Chemistry in Chemical Protein Synthesis

Imine chemistry has found multiple applications in the synthesis of highly complex protein targets. In contrast to native chemical ligation methods that will solely result in natural elements, end-products of orthogonal imine chemistry will result in one or more non-natural elements being incorporated in the desired protein target. This chapter will focus on three aspects necessary to employ imine ligation in total protein synthesis. First, functionalization methods are described necessary to introduce carbonyl, aminooxy or hydrazide functionalities in a polypeptide chain. Next, applications of various imine ligation strategies (oxime, hydrazone, Pictet-Spengler) in the field of protein chemistry are reviewed. Finally, methods to catalyse these reactions are summarized.