THE DEPSIPEPTIDE METHODOLOGY: APPLICATION TO EXCEPTIONALLY DIFFICULT SEQUENCES AND DEVELOPMENT OF AN AUTOMATED TECHNIQUE VIA DEPSIDIPEPTIDE UNITS

摘要

A peptide sequence that is difficult to synthesize because of aggregation phenomena can be more easily obtained through its depsipeptide analogue, which is assembled by extending the growing peptide chain, from a suitable point on, via the β-hydroxyl function of a Ser/Thr residue. The discontinuity introduced in the regular pattern of amide bonds by the presence of a depsi unit affects the tendency of the peptide to fold, thus providing in most cases an improvement in synthetic efficiency. Moreover, after cleavage of the peptide from the solid support, each depsipeptide unit provides an additional ionizable moiety, thereby increasing solubility and facilitating purification. The conversion to the target amide peptide is smoothly achieved through an O,N-acyl shift, which occurs quantitatively under mildly basic conditions over a short period of time.