Aggregation of resin‐bound peptides during solid‐phase peptide synthesis: Prediction of difficult sequences

Nonrandom incomplete aminoacylation of a pendent peptide chain on an insoluble polymeric support during solid‐phase peptide synthesis is sequence‐dependent and is caused by aggregation of peptide chains, manifested by a decreased swelling capacity. The volume of the swollen peptidyl‐resin after each coupling during the syntheses of 87 sequence unrelated peptides was measured, and for each amino acid an aggregation parameter, 〈P_a〉, was derived that reflects the propensity of the swollen volume of peptidyl‐resin to decrease during peptide synthesis. These aggregation parameters were used to predict potentially difficult sequences.