title: The importance of structural factors on the rate and the extent of N,O-acyl migration in cyclic and linear peptides.
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.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas Lawrence 66045, USA.
authors.forename: R
authors.initials: R
authors.lastname: Oliyai
authors.forename: T J
authors.initials: TJ
authors.lastname: Siahaan
authors.forename: V J
authors.initials: VJ
authors.lastname: Stella
mesh_terms: D003500:Cyclization; D016572:Cyclosporine / Q000737:chemistry*; D003524:Cyclosporins / Q000737:chemistry*; D007700:Kinetics; D008745:Methylation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D003524:Cyclosporins; D010455:Peptides; C100000:cyclosporin C; D016572:Cyclosporine