In Situ Neutralization Protocols for Boc-SPPS

Significant effort has been devoted to the optimization of solid-phase peptide synthesis (SPPS) to maximize the process to facilitate the synthesis of a desired peptide sequence, without extensive optimization or resynthesis. Over the last 25 years, a set of synthetic protocols developed by Kent and Alewood has proven to be robust and efficient for Boc/Bzl SPPS and has been widely adopted by the research community. In this chapter, we describe a variation of manual in situ neutralization protocols for Boc-SPPS that are highly effective for the rapid synthesis of peptides with different C-terminal functionalities.