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

J Pept Sci. 2014 Apr;20(4):235-9. doi: 10.1002/psc.2624. Epub 2014 Mar 6.

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.

Keywords: cyclic peptide; discontinuous epitope; orthogonal functionalization; protein mimic; scaffold; sequential cycloaddition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry
  • Azides / chemistry*
  • Bacterial Outer Membrane Proteins / chemistry*
  • Bordetella pertussis / chemistry*
  • Copper / chemistry*
  • Cycloaddition Reaction*
  • Molecular Mimicry*
  • Peptides, Cyclic / chemical synthesis*
  • Spectrometry, Mass, Electrospray Ionization
  • Virulence Factors, Bordetella / chemistry*

Substances

  • Alkynes
  • Azides
  • Bacterial Outer Membrane Proteins
  • Peptides, Cyclic
  • Virulence Factors, Bordetella
  • pertactin
  • Copper