Improved Tag-Assisted LPPS: An Application to the Synthesis of Bradykinin Receptor-Antagonist Icatibant Acetate

A cost- and time-effective synthetic method is a prerequisite to producing therapeutic peptides on a commercial scale. Herein, we demonstrate that a soluble tag-assisted liquid-phase peptide synthesis using a hydrophobic benzyl alcohol as a support is applicable to the 100 g scale production of therapeutic peptides, using bradykinin receptor-antagonist icatibant acetate as a model. The use of sacrificial propylamine to trap the activated amino acids enables one-pot sequential couplings and deprotections without detectable double hits. By using the modified procedure, precipitations at every other step are sufficient for the overall process, significantly reducing the amount of MeCN required. The complete consumption ( 99%).