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 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

DOI: 10.1007/s00726-011-0887-1

Cite this article as:
De Santis, E., Hjelmgaard, T., Faure, S. et al. Amino Acids (2011) 41: 663. doi:10.1007/s00726-011-0887-1

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

Peptidomimeticsα,β-peptoidsCircular dichroismX-ray crystallography

Abbreviations

CD

Circular dichroism

COSY

Proton–proton correlation experiment

DMAP

4-Dimethylaminopyridine

DMF

N,N-Dimethylformamide

EDC

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

HATU

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

HFIP

1,1,1,3,3,3-Hexafluoroisopropanol

HMBC

Heteronuclear multiple bond correlation experiment

HRMS

High-resolution mass spectroscopy

HSQC

Heteronuclear single quantum correlation experiment

IR

Infrared

NMR

Nuclear magnetic resonance

rt

Room temperature

SI

Supporting information

SRCD

Synchrotron radiation circular dichroism

TFA

Trifluoroacetic acid

TFE

2,2,2-trifluoroethanol

THF

Tetrahydrofuran

TLC

Thin layer chromatography

UV

Ultraviolet

Supplementary material

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

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