Amino Acids

, Volume 41, Issue 3, pp 663–672 | Cite as

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

  • Emiliana De Santis
  • Thomas Hjelmgaard
  • Sophie Faure
  • Olivier Roy
  • Claude Didierjean
  • Bruce D. Alexander
  • Giuliano Siligardi
  • Rohanah Hussain
  • Tamás Jávorfi
  • Alison A. Edwards
  • Claude Taillefumier
Original Article


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.


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



Circular dichroism


Proton–proton correlation experiment






1-(3-Dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride


O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate




Heteronuclear multiple bond correlation experiment


High-resolution mass spectroscopy


Heteronuclear single quantum correlation experiment




Nuclear magnetic resonance


Room temperature


Supporting information


Synchrotron radiation circular dichroism


Trifluoroacetic acid






Thin layer chromatography





We gratefully thank the Carlsberg Foundation for a grant to TH and Aurélie Job and Bertrand Légeret (Clermont-Université, Laboratoire SEESIB) for HPLC and mass spectrometry analysis. AAE gratefully acknowledges the beam time awarded from the Diamond Light Source, UK for the circular dichroism beamline B23. We are greatly indebted to technical team of the “Plateforme de mesures de diffraction X” of the CRM2 (Université de Lorraine).

Supplementary material

726_2011_887_MOESM1_ESM.pdf (1.5 mb)
Supplementary material 1 (PDF 1.54 MB)


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Emiliana De Santis
    • 1
  • Thomas Hjelmgaard
    • 2
    • 3
  • Sophie Faure
    • 2
    • 3
  • Olivier Roy
    • 2
    • 3
  • Claude Didierjean
    • 4
  • Bruce D. Alexander
    • 5
  • Giuliano Siligardi
    • 6
  • Rohanah Hussain
    • 6
  • Tamás Jávorfi
    • 6
  • Alison A. Edwards
    • 1
  • Claude Taillefumier
    • 2
    • 3
  1. 1.Medway School of PharmacyUniversities of Kent and Greenwich at MedwayChatham MaritimeUK
  2. 2.Clermont-Université, Université Blaise Pascal, Laboratoire SEESIBClermont-FerrandFrance
  3. 3.CNRS, UMR 6504, Laboratoire SEESIBAubière CedexFrance
  4. 4.CRM2, Equipe Biocristallographie, UMR 7036 CNRS-UHP, Faculté des Sciences et TechnologiesUniversité de LorraineVandoeuvre-lès-NancyFrance
  5. 5.School of ScienceUniversity of GreenwichChatham MaritimeUK
  6. 6.Diamond Light Source Ltd., Diamond House, Harwell Science and Innovation CampusDidcotUK

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