Pseudoproline dipeptides consist of a dipeptide in which the Ser or Thr residue has been reversibly protected as proline-like TFA-labile oxazolidine. The insertion of a pseudoproline dipeptide into a sequence disrupts the formation of the secondary structures thought responsible for problems during peptide assembly, leading to better and more predictable acylation and deprotection kinetics. The most dramatic results are seen in the preparation of highly aggregated sequences, where 10-fold increases in product yield have been achieved from insertion of a single pseudoproline. However, the enhanced and more uniform reaction rates also benefit routine synthesis, providing improved yields, purities and solubilities of crude products, and easier HPLC purification with higher product return. For longer peptides, the incorporation of several pseudoprolines at regular intervals throughout the sequence has been found to be particularly effective.
