Liquid Phase Synthesis of Peptides

Abstract

ONE of the most exciting recent developments in peptide synthesis is the introduction of the solid phase method¹ which facilitates rapid synthesis of peptides by the elimination of tedious purification steps. Excess reagents are removed by filtration. The ease of these operations led to speculations that the method might be used for the synthesis of enzymes, but careful investigation has shown that the individual coupling steps are not quantitative, so that erroneous sequences accumulate, together with the desired poly peptide^2,3. General methods to separate such complex mixtures are still not available, especially if the chain length exceeds 20 amino-acids, so much was clear in the attempted synthesis of the enzyme ribonuclease⁴ and other larger peptides. Another disadvantage of the solid phase method compared with synthesis in solution is the restriction in the choice of solvents, coupling methods and protecting groups.