Original Article

Amino Acids

, Volume 41, Issue 3, pp 663-672

Cyclic α,β-peptoid octamers with differing side chain patterns: synthesis and conformational investigation

  • Emiliana De SantisAffiliated withMedway School of Pharmacy, Universities of Kent and Greenwich at Medway
  • , Thomas HjelmgaardAffiliated withClermont-Université, Université Blaise Pascal, Laboratoire SEESIBCNRS, UMR 6504, Laboratoire SEESIB
  • , Sophie FaureAffiliated withClermont-Université, Université Blaise Pascal, Laboratoire SEESIBCNRS, UMR 6504, Laboratoire SEESIB
  • , Olivier RoyAffiliated withClermont-Université, Université Blaise Pascal, Laboratoire SEESIBCNRS, UMR 6504, Laboratoire SEESIB
  • , Claude DidierjeanAffiliated withCRM2, Equipe Biocristallographie, UMR 7036 CNRS-UHP, Faculté des Sciences et Technologies, Université de Lorraine
  • , Bruce D. AlexanderAffiliated withSchool of Science, University of Greenwich
  • , Giuliano SiligardiAffiliated withDiamond Light Source Ltd., Diamond House, Harwell Science and Innovation Campus
  • , Rohanah HussainAffiliated withDiamond Light Source Ltd., Diamond House, Harwell Science and Innovation Campus
  • , Tamás JávorfiAffiliated withDiamond Light Source Ltd., Diamond House, Harwell Science and Innovation Campus
    • , Alison A. EdwardsAffiliated withMedway School of Pharmacy, Universities of Kent and Greenwich at Medway Email author 
    • , Claude TaillefumierAffiliated withClermont-Université, Université Blaise Pascal, Laboratoire SEESIBCNRS, UMR 6504, Laboratoire SEESIB Email author 

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Abstract

The solution-phase synthesis and cyclisation of three α,β-peptoid octamers with differing side chain patterns is reported. One of these, compound C, showed a significantly greater resolution by NMR relative to the other two structurally related octamers. This observation was studied in detail by circular dichroism at a synchrotron light source to facilitate the correlation between the side chain patterns and conformational preference of these three peptoids. The X-ray crystal structure of cyclic octamer C, the first high-resolution structure for the α,β-peptoid backbone, was also obtained from methanol. Combined solid- and solution-phase studies allowed the identification of the N-2-(benzyloxy)ethyl side chain on the β-residue of the heterogeneous backbone as a key structural feature driving the increased conformational stability for octamer C.

Keywords

Peptidomimetics α,β-peptoids Circular dichroism X-ray crystallography