Industrial applications of solid-phase peptide synthesis - A status report

Despite the fact that the structure of peptides has been known for more than a century, it was not until du Vigneaud published the synthesis of oxytocin 50 years later that the field was truly launched and the use of peptides as pharmaceuticals began. Since then, technical progress in the field has been astonishing, and the synthesis of peptides of virtually any size and complexity is now possible, with scale-up to the level of metric tonnes a reality. Perhaps the most important development was Merrifield's publication of the solid-phase peptide synthesis (SPPS) method, which completely revolutionized the field, both from the perspective of accelerating research and discovery, and also because of its now widespread use for the manufacture of peptides for use as active pharmaceutical ingredients (APIs). The application of the SPPS method to the manufacture of peptide APIs will be reviewed, including both a historical overview and a summary of the current status. Some of the remaining challenges will also be discussed.