Studies in solid-phase peptide synthesis: a personal perspective

By the early 1970s it had became apparent that the solid-phase synthesis of ribonuclease A could not be generalized. Consequently, virtually every aspect of solid-phase peptide synthesis (SPPS) was reexamined and improved during the decade of the 1970s. The sensitive detection and elimination of possible side reactions (amino acid insertion, N(alpha)-trifluoroacetylation, N(alphaepsilon)-alkylation) were examined. The quantitation of coupling efficiency in SPPS as a function of chain length was studied. A new and improved support for SPPS, the "PAM-resin," was prepared and evaluated. These and many other studies from the Merrifield laboratory and elsewhere increased the general acceptance of SPPS leading to the 1984 Nobel Prize in Chemistry for Bruce Merrifield.