Solvation of the Polymer Matrix. Source of Truncated and Deletion Sequences in Solid Phase Synthesis

An automated procedure utilizing hydrogen chloride-36 for monitoring the free amine in automated solid phase synthesis was developed. Discrepancies were found between the values determined by this procedure and those from amino acid analysis in the synthesis of a peptide, residues 63-74, of acyl carrier protein. These results led to a hypothesis of dynamic solvation changes of the polymer matrix as synthesis proceeds. The effects of chain termination by acetylation were also in agreement with the hypothesis. Dynamic solvation changes of the polymer matrix leads to the sequence-dependent problems of solid phase synthesis, both truncated and deletion sequences. It may also be responsible for difficulties encountered with monitoring procedures and with attempts to terminate unreacted peptide chains. Based on these observations, a modified procedure of solid phase peptide synthesis was developed which significantly improved the synthesis of residues 63-74 of acyl carrier protein.