THE IMPORTANCE OF STRUCTURAL FACTORS ON THE RATE AND THE EXTENT OF N,O-ACYL MIGRATION IN CYCLIC AND LINEAR PEPTIDES

The chemistry associated with the process of N,O-acyl migration was ex plored in both cyclic and linear peptides under aqueous acid condition s. The importance of backbone cyclization and N-methylation of the pep tide bond on the kinetics of N,O-acyl migration in a series of linear and cyclic peptides related in structure to cyclosporin A (CsA) were e xamined. The similarity in the chemical reactivity of the cyclic pepti de [MeLeu (3-OH)](1)-CsA and the corresponding linear peptide [Val-MeL eu (3-OH)-Abu], suggested that for this series, cyclization of the pep tide backbone may not play an important role in controlling the kineti cs of N,O-acyl migration. In contrast, the disparity in the chemical r eactivity of tripeptides [Val-MeLeu (3-OH)-Abu] and [Val-Leu (3-OH)-Ab u], indicated that N-methylation of amide bond significantly impacted the kinetics. Various hypothesis are proposed to account for this obse rvation.