Probing Peptidylprolyl Bond cis/trans Status Using Distal 19F NMR Reporters

Patrick M. Killoran, George S. M. Hanson, Sanne J. M. Verhoork, Madeleine Smith, Davide Del Gobbo, Lu-Yun Lian, Christopher R. Coxon

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
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A method for measuring peptidylprolyl bond cis-trans conformational status in peptide models is described, using 4-fluorophenylalanine (4FPhe) as a distal reporter for 19F NMR. The %cis-Pro population was measured for peptides of the general structure Ac-X-Pro-Z-Ala-Ala-4FPhe (X and Z are proteinogenic amino acids) at pH 7.4, and provided conformational populations consistent with literature values obtained by more complex methods. This approach was applied to probe the prolyl bond status in pentapeptide models of the intrinsically disordered C-terminal region of α-synuclein, which mirrored the preferences in the Ac-X-Pro-Z-Ala-4FPhe models. Advantageously, the 19F reporter group does not need to be adjacent to or attached to proline to provide quantifiable signals and distal 4-fluorophenylalanines can be placed so as not to influence prolyl bond conformation. Finally, we demonstrated that the prolyl bond status is not significantly affected by pH when there are ionisable amino acid residues at the carboxyl side of proline, which makes 19F NMR an invaluable tool with which to study proline isomerism at a range of pHs and in different solvents and buffers.
Original languageEnglish
Article numbere202203017
JournalChemistry - A European Journal
Issue number16
Early online date16 Feb 2023
Publication statusPublished - 16 Mar 2023


  • F NMR
  • fluorinated amino acids
  • peptides
  • proline conformation

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry


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