3 - Peptide Synthesis: A Review of the Solid-Phase Method

Abstract

This chapter discusses the biological roles and the chemical structures of an increasing number of peptide and protein hormones. The increased visibility of peptides gives impetus to peptide synthesis. Solid-phase peptide synthesis offers many advantages over conventional solution synthesis because of the simplicity of operation and dramatic savings in time. The method provides the ideal means for peptide and protein synthesis. Solid-phase peptide synthesis has found numerous applications not only by peptide chemists but also by biochemists, biologists, pharmacologists, physiologists, endocrinologists, and immunologists. There are four efficient methods of peptide bond formation which have found a wide and general application: the azide method, the mixed anhydride method, the dicyclohexylcarbodiimide method, and the active ester method. The chapter also discusses two principal strategies for assembling all amino acid residues into the desired peptide sequence: fragment condensation and incremental chain elongation. Fragment condensation allows greater flexibility in the choice of protecting groups and condensing methods but is impeded by the danger of racemization at the carbon of the C-terminal amino acid in the carboxyl component.