Flow-based SPPS for protein synthesis: A perspective

Abstract

Flow‐based approaches to solid phase peptide synthesis (SPPS) have been pursued since the method's early days, with anticipated gains in speed, reaction monitoring, and ease of automation. Here, we discuss how these advantages are being realized by synthesis at elevated temperature, facilitated by a 'preheat/activation' loop. This important modification both accelerates peptide synthesis—providing a wealth of new data from in‐line monitoring—and in conjunction with an optimized protocol, extends the length of peptides routinely accessible by stepwise synthesis. Streamlined synthesis of longer peptides will address a major challenge in chemical protein synthesis: preparation of peptide segments for use in chemical ligation. The context of recent results in flow‐based SPPS is discussed, highlighting remaining challenges and future opportunities.