Isoacyl dipeptides are remarkable new tools for enhancing synthetic efficiency in Fmoc SPPS. Substitution of Aaa-Ser or Aaa-Thr in a peptide sequence with an isoacyl dipeptide results in the formation of a depsipeptide analog of the native sequence in which the amide bond between Aaa and Ser or Thr is replaced by an ester linkage. This modification results in a marked change in the conformation of the peptide chain which leads to disruption of aggregation in much the same way as would insertion of a pseudoproline or N-Dmb/Hmb-residue. However, the real benefits of using isoacyl dipeptides become apparent once the peptide is released from the solid phase. In contrast to pseudoproline dipeptides, the product cleaved when using isoacyl dipeptides is the depsipeptide and not the native peptide sequence. Such depsipeptide analogs of aggregation prone peptides have been found to be more soluble and consequently more easily purified than the highly structured native peptide.