Quick Access to High-Purity Peptide Drugs Bradykinin, Leuprolide Analogue, 2(PZ-128), and Rapastinel with Minimal Reagents

Abstract

Peptide drugs bradykinin, a leuprolide analogue, 2(PZ-128), and rapastinel are synthesized in 56-77% yield using heating-assisted liquid-phase peptide synthesis on a soluble polynorbornene support. These drugs of commercial utility and complex structures are obtained in 2-5.5 h with no epimerization and >95% purity using only 1.2 equivalents of amino acids and coupling reagents. The peptide yield and purity are comparable or superior to the reported methods.