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Amino Acids

, Volume 38, Issue 1, pp 213–222 | Cite as

Antifreeze glycopeptide analogues: microwave-enhanced synthesis and functional studies

  • Carolin Heggemann
  • Carsten Budke
  • Benjamin Schomburg
  • Zsuzsa Majer
  • Marco Wißbrock
  • Thomas Koop
  • Norbert SewaldEmail author
Original Article

Abstract

Antifreeze glycoproteins enable life at temperatures below the freezing point of physiological solutions. They usually consist of the repetitive tripeptide unit (-Ala-Ala-Thr-) with the disaccharide α-d-galactosyl-(1–3)-β-N-acetyl-d-galactosamine attached to each hydroxyl group of threonine. Monoglycosylated analogues have been synthesized from the corresponding monoglycosylated threonine building block by microwave-assisted solid phase peptide synthesis. This method allows the preparation of analogues containing sequence variations which are not accessible by other synthetic methods. As antifreeze glycoproteins consist of numerous isoforms they are difficult to obtain in pure form from natural sources. The synthetic peptides have been structurally analyzed by CD and NMR spectroscopy in proton exchange experiments revealing a structure as flexible as reported for the native peptides. Microphysical recrystallization tests show an ice structuring influence and ice growth inhibition depending on the concentration, chain length and sequence of the peptides.

Keywords

Bioorganic chemistry Microwave synthesis Glycopeptides Recrystallization Circular dichroism 

Abbreviations

AFGP

Antifreeze glycopeptide

AFP

Antifreeze protein

br

Broad

CD

Circular dichroism

DIPEA

N,N-Diisopropylethylamine

DMF

N,N-Dimethylformamide

EtOAc

Ethyl acetate

Fmoc

N-(9H-Fluoren-9-yl)-methoxycarbonyl

GalNAc

2-Acetamido-2-deoxy-d-galactopyranosyl-

HATU

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

HOAt

1-Hydroxy-7-azabenzotriazole

MeOH

Methanol

HOBt

1-Hydroxybenzotriazole

NaOMe

Sodium methoxide

NMP

1-Methyl-2-pyrrolidone

TBTU

O-(Benzotriazol-1-yl)-N,N,N’,N’-tetramethyluronium tetrafluoroborate

TFA

Trifluoroacetic acid

TFE

2,2,2-Trifluoroethanol

Notes

Acknowledgments

The authors gratefully acknowledge support from DFG (SFB 613).

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Carolin Heggemann
    • 1
  • Carsten Budke
    • 2
  • Benjamin Schomburg
    • 1
  • Zsuzsa Majer
    • 3
  • Marco Wißbrock
    • 1
  • Thomas Koop
    • 2
  • Norbert Sewald
    • 1
    Email author
  1. 1.Organic and Bioorganic ChemistryBielefeld UniversityBielefeldGermany
  2. 2.Physical ChemistryBielefeld UniversityBielefeldGermany
  3. 3.Institute of ChemistryEötvös UniversityBudapestHungary

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