Chapter 5 - Differential Protection and Selective Deprotection in Peptide Synthesis

Abstract

This chapter discusses differential protection and selective deprotection in peptide synthesis. The assembling of amino acid residues into defined polypeptide chains without protecting groups is possible in biosynthetic processes. In this case, apart from the correct template sequence of nucleotides, it requires impressive biosynthetic machinery. In the laboratory of the peptide chemist, a minimal recourse to protecting groups is necessary. However, this cumbersome detour permits the correct synthesis of defined sequences of natural or even unnatural amino acids. There is still no ideal blocking group that is introduced easily and without racemization and that is stable during synthesis but readily removed at any desired step. There are no completely satisfactory protection means for the side chains of arginine and histidine, so intense research is still needed in these fields. A serious problem is associated with the change of solubility of the lengthening chain, partly because of the presence of protecting groups. Differential protection and selective deprotection—also largely employed for the chemical synthesis of polynucleotides—still remain the only efficient tools for the production of unequivocally defined polypeptides.