title: Versatile convergent synthesis of a three peptide loop containing protein mimic of whooping cough pertactin by successive Cu(I)-catalyzed azide alkyne cycloaddition on an orthogonal alkyne functionalized TAC-scaffold.
abstract: Synthetic mimics of discontinuous epitopes may have a wide range of potential applications, including synthetic vaccines and inhibition of protein-protein interactions. However, synthetic access to these relatively complex peptide molecular constructs is limited. This paper describes a versatile convergent strategy for the construction of protein mimics presenting three different cyclic peptides. Using an orthogonal alkyne protection strategy, peptide loops were introduced successively onto a triazacyclophane scaffold via Cu(I)-catalyzed azide alkyne cycloaddition. This method provides rapid access to protein mimics requiring different peptide segments for their interaction and activity.
authors.affiliation: Division of Medicinal Chemistry & Chemical Biology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, PO Box 80082, 3508 TB, Utrecht, The Netherlands.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Werkhoven
authors.forename: Helmus
authors.initials: H
authors.lastname: van de Langemheen
authors.forename: Steffen
authors.initials: S
authors.lastname: van der Wal
authors.forename: John A W
authors.initials: JA
authors.lastname: Kruijtzer
authors.forename: Rob M J
authors.initials: RM
authors.lastname: Liskamp
mesh_terms: D000480:Alkynes / Q000737:chemistry; D001386:Azides / Q000737:chemistry*; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry*; D001886:Bordetella pertussis / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D061565:Cycloaddition Reaction; D018716:Molecular Mimicry; D010456:Peptides, Cyclic / Q000138:chemical synthesis*; D021241:Spectrometry, Mass, Electrospray Ionization; D010566:Virulence Factors, Bordetella / Q000737:chemistry*
chemical_list: D000480:Alkynes; D001386:Azides; D001425:Bacterial Outer Membrane Proteins; D010456:Peptides, Cyclic; D010566:Virulence Factors, Bordetella; C068929:pertactin; D003300:Copper
keywords: cyclic peptide; discontinuous epitope; orthogonal functionalization; protein mimic; scaffold; sequential cycloaddition