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, <Pa>, 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.