Prep/Semiprep separations of peptides.

Abstract

Peptide synthesis has undergone a major transformation in the last three decades, building on the solid-phase synthesis methodology of Bruce Merrifield first published in 1963 (1). During the 1970s, the first automation of peptide synthesis was undertaken using Boc chemistry. In the 1980s, improvements were made in the Boc chemistry automated process and, consequently, the synthesis of more-difficult sequences, as well as longer polypeptides became possible (2). Solid-phase Fmoc synthesis was developed in the early 1980s (3,4) and was also applied to automated systems (5). The 1990s saw improvements in both Boc and Fmoc chemistry together with novel modes of activation of the amino acids in both chemistries (6,7). The result was faster cycle times and, hence, reduced synthesis times. The range of protecting groups and resins available today means that sophisticated syntheses utilizing a combination of Boc and Fmoc chemistry are possible (8).