R. Oliyai et al., THE IMPORTANCE OF STRUCTURAL FACTORS ON THE RATE AND THE EXTENT OF N,O-ACYL MIGRATION IN CYCLIC AND LINEAR PEPTIDES, Pharmaceutical research, 12(3), 1995, pp. 323-328
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.