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Glycoconjugate Journal

, Volume 24, Issue 2–3, pp 157–165 | Cite as

Conjugation of oligosaccharides by reductive amination to amine modified chondroitin oligomer and γ-cyclodextrin

  • Krista Weikkolainen
  • Olli Aitio
  • Maria Blomqvist
  • Jari Natunen
  • Jari Helin
Article

Abstract

Carbohydrates present on cell surfaces participate in numerous biological recognition phenomena including cell–cell interactions, cancer metastasis and pathogen invasion. Therefore, synthetic carbohydrates have a potential to act as pharmaceutical substances for treatment of various pathological phenomena by inhibiting specifically the interaction between cell surface carbohydrates and their protein receptors (lectins). However, the inherently low affinity of carbohydrate-protein interactions has often been an obstacle for successful generation of carbohydrate based pharmaceuticals. Multivalent glycoconjugates, i.e. structures carrying several copies of the active carbohydrate sequence in a carrier molecule, have been constructed to overcome this problem. Here we present two novel types of multivalent carbohydrate conjugates based on chondroitin oligomer and cyclodextrin carriers. These carriers were modified to express primary amino groups, and oligosaccharides were then bound to carrier molecules by reductive amination. Multivalent conjugates were produced using the human milk type oligosaccharides LNDFH I (Lewis-b hexasaccharide), LNnT, and GlcNAcβ1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc.

Keywords

Chondroitin sulphate A γ-CD Reductive amination Multivalent oligosaccharides 

Abbreviations

Ch14

chondroitin 14-mer

CMP-Neu5Ac

cytidine 5′-monophospho-5-N-acetyl neuraminic acid)

CS

chondroitin sulphate

DAP

1,3-diaminopropane

DAP-Ch14

1,3-diaminopropane amidated chondroitin 14-mer

DAP-ox-γ-CD

oxidized and 1,3-diaminopropane amidated γ-cyclodextrin

DIPEA

N-ethyldiisopropylamine

DMSO

dimethyl sulphoxide

γ-CD

γ-cyclodextrin

pNP-β-GlcA

para-nitrophenyl-β-glucuronide

GnLacNAcLac

GlcNAcβ1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc

HBTU

2-(1H-bentsotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphatel

LNDFH I

Fucα1-2Galβ1-3(Fucα1-4)GlcNAcβ1-3Galβ1-4Glc

LNnT

Galβ1-4GlcNAcβ1-3Galβ1-4Glc

MALDI-TOF MS

matrix-assisted laser desorption-ionization time-of-flight mass spectrometry

MES

morpholinoethane sulphonate

ox-γ-CD

oxidized γ-cyclodextrin

SA

sialyl

TEMPO

tetramethylpiperidine-1-oxy radical

Notes

Acknowledgement

An early contribution of Biotie Therapies Corp. is gratefully acknowledged. We thank Dr. Ritva Niemelä and Dr. Anne Olonen, and Tero Satomaa for critical reading of the manuscript. This work was supported by The Technology Development Center of Finland, the Emil Aaltonen Foundation, and Foundation of Magnus Ehrnrooth.

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Krista Weikkolainen
    • 1
  • Olli Aitio
    • 2
  • Maria Blomqvist
    • 3
  • Jari Natunen
    • 3
  • Jari Helin
    • 3
  1. 1.Department of Biological and Environmental SciencesUniversity of HelsinkiHelsinkiFinland
  2. 2.Drug Discovery and Development Technology CenterUniversity of HelsinkiHelsinkiFinland
  3. 3.Glykos Finland Ltd.HelsinkiFinland

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