NF-31 color test uncovers ‘hidden’ alcohol functionalities in PEG-based resins for solid phase peptide synthesis

Recently developed PEG-based resins have been shown to markedly improve the quality of the synthesis in case of the so-called ‘difficult’ peptide sequences. Difficult coupling reactions further require sensitive color tests for amines in the assessment of the completeness of coupling. We here describe how the use of PEG-based resins in combination with one of the more sensitive color tests in SPPS can lead to severe misinterpretation and unnecessary delays during solid phase peptide synthesis due to the presence of ‘non-declared’ free hydroxyl functionalities in aminomethyl-PEG-based resins.