Thermodynamic binding studies of cell surface carbohydrate epitopes to galectins-1, -3, and -7: Evidence for differential binding specificities

Nisar Ahmad, Hans J. Gabius, Herbert Kaltner, Sabine André, Ichiro Kuwabara, Fu Tong Liu, Stefan Oscarson, Thomas Norberg, C. Fred Brewer

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Abstract

Binding of a series of sialylated and non-sialylated cell surface carbohydrates to bovine heart galectin-1, recombinant murine galectin-3, and recombinant human galectin-7 was investigated by isothermal titration microcalorimetry (ITC) and hemagglutination inhibition measurements. Galectin-7 shows nearly equal affinities for lactose and Galβ (1-4)GlcNAc (LacNAc-II). Galectin-7, however, displays six- and 11-fold weaker affinity for LacNAc-II compared with galectins-1 and -3, respectively. The affinity of galectin-7 for LacNAc-II containing oligosaccharides is also weaker than the other two galectins. ITC measurements show that all three galectins bind to di- and trimeric oligomers of LacNAc-II, which are epitopes found in poly-N-acetyllactosamine chains of glycoprotein receptors, with affinity constants similar to that of LacNAc-II. The binding valencies of the di- and trimeric LacNAc-II oligomers were observed to be one from ITC measurements, indicating formation of 1:1 complexes with all three galectins. Thus, galectins-1, -3, and -7 all possess binding sites that primarily accommodate one LacNAc-II moiety per monomer of protein. Sialylated oligosaccharides show different specificities for the three galectins. While 2,3-sialyl LacNAc-II binds to all three galectins, 2,6-sialyl LacNAc-II fails to bind to any of the galectins; 2,6-sialylated diLacNAc binds well to galectin-3 and galectin-7, but only weakly to galectin-1. Similar results are obtained with 2,6-sialyl lacto-N-neo-tetraose, which has a reducing end lactose moiety. Thus, unlike galectin-1, which predominantly recognizes non-reducing terminal LacNAc-II residues in oligosaccharides, galectins-3 and -7 recognize both non-reducing terminal LacNAc-II residues as well as internal LacNAc-II and lactose residues in sialylated and non-sialylated oligosaccharides.

Original languageEnglish (US)
Pages (from-to)1096-1104
Number of pages9
JournalCanadian Journal of Chemistry
Volume80
Issue number8
DOIs
StatePublished - Dec 3 2002

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Keywords

  • Binding specificities
  • Carbohydrates
  • Galectins
  • Isothermal titration microcalorimetry
  • Lectins

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Organic Chemistry

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