Optimizing TFA Peptide Rink Amide Resin Acidolysis Using Hydrogen Chloride

We report an optimization of the standard acidolysis release of peptides from Rink Amide aminomethyl (RA-AM) resin using a combination of trifluoroacetic acid (TFA) and concentrated aqueous hydrogen chloride. The standard TFA-based protocol often leads to incomplete cleavage and reduced peptide yields. Addition of small percentages of HCl to TFA furnishes practically quantitative cleavage yields, improving overall efficiency and reproducibility. Yield improvements between 9 and 52% have been accomplished.