Swellographic Study of Peptide Resin Swelling Behavior during Solid Phase Peptide Synthesis

A representative array of peptide resin swelling data obtained using swellographic monitoring technique was analyzed to determine general tendencies in swelling volume dynamics in the course of Boc- and Fmoc-SPPS. Efficiency of the approach based on analyzing swelling volume changes (ΔV) as a function of nominal molecular weight change (ΔM) of the pendant peptide chain was demonstrated. The conclusion was made that a linear relationship between swelling volume and weight changes of peptide resin is a normal basic trend in line with results of early model studies carried out by Merrifield and coworkers. Excellent linear ΔV vs. ΔM correlations (r > 0.97) throughout SPPS for peptide resins swollen in DMF appeared to be typical of >60% of analyzed peptides and also are invariably observed for incorporation of the first four C-terminal amino acids and Boc-deprotected peptide resins swollen in 50% TFA-DCM. Formal theoretical interpretation of the observed regularities and anomalies of swelling volume dynamics and related solvation changes was made in terms of solvation numbers defined as a number of solvent molecules associated with a specific molecular segment of peptide-resin.