Improved acidolytic deprotection conditions for the Fmoc-based solid-phase synthesis of thioxo peptides

The acid-mediated cleavage of a synthetic thioxo peptide was monitored using deprotection cocktails with varying concentrations of TFA. Thioxo peptides are acid labile, undergoing cleavage at the amide linkage immediately following the thioamide linkage in the sequence. This acid lability makes Fmoc-based synthesis the method of choice for thioxo peptide preparation. The extent of cleavage increases with increased TFA concentration and longer reaction time. Data presented herein indicate that deprotection protocols involving low TFA concentration (ca. 80%) and short reaction times (ca. 2 h) minimize the losses due to acidolytic cleavage.