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Pharmaceutical Research

, Volume 12, Issue 3, pp 323–328 | Cite as

The Importance of Structural Factors on the Rate and the Extent of N,O-acyl Migration in Cyclic and Linear Peptides

  • Reza Oliyai
  • Teruna J. Siahaan
  • Valentine J. Stella
Article

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.

acyl migration peptides cyclosporin stability 

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Copyright information

© Plenum Publishing Corporation 1995

Authors and Affiliations

  • Reza Oliyai
    • 1
  • Teruna J. Siahaan
    • 1
  • Valentine J. Stella
    • 1
  1. 1.Department of Pharmaceutical ChemistryThe University of KansasLawrence

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