Abstract
The chemistry associated with the process of N,O-acyl migration was explored in both cyclic and linear peptides under aqueous acid conditions. The importance of backbone cyclization and N-methylation of the peptide 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 examined. The similarity in the chemical reactivity of the cyclic peptide [MeLeu (3-OH)]1-CsA and the corresponding linear peptide [Val-MeLeu (3-OH)-Abu], suggested that for this series, cyclization of the peptide backbone may not play an important role in controlling the kinetics of N,O-acyl migration. In contrast, the disparity in the chemical reactivity of tripeptides [Val-MeLeu (3-OH)-Abu] and [Val-Leu (3-OH)-Abu], indicated that N-methylation of amide bond significantly impacted the kinetics. Various hypothesis are proposed to account for this observation.
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Oliyai, R., Siahaan, T.J. & Stella, V.J. The Importance of Structural Factors on the Rate and the Extent of N,O-acyl Migration in Cyclic and Linear Peptides. Pharm Res 12, 323–328 (1995). https://doi.org/10.1023/A:1016231913858
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DOI: https://doi.org/10.1023/A:1016231913858