High resolution proton NMR studies of gangliosides. Structure of two types of G(D3) lactones and their reactivity with monoclonal antibody R24

S. Ando, Robert K Yu, J. N. Scarsdale, S. Kusunoki, J. H. Prestegard

Research output: Contribution to journalArticle

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Abstract

Gangioside G(D3) was converted at room temperature to two stable lactones, denoted as G(D3) lactones I and II. The reaction sequence was presumed to be G(D3) → G(D3) lactone I → G(D3) lactone II based on the time course of their production. Lactone I behaved as a monosialoganglioside and lactone II as a neutral species. The two lactones were isolated by DEAE-Sephadex column chromatography. The positions of the inner ester linkages were investigated by two-dimensional J-correlated proton NMR spectroscopy. An ester linkage was most likely formed between the carboxyl group of the external sialic acid residue and C9-OH of the internal sialic acid residue in lactone I. In addition to this ester linkage, a second ester linkage between the carboxyl group of the internal sialic acid and C2-OH of the galactose residue was likely formed in lactone II. The structural changes induced by lactonization were further examined by their reactivity with the monoclonal antibody R24 (Puckel, C.S., Lloyd, K.O., Travassos, L.R., Dippold, W.G., Oettgen, H.F., and Old, L.J. (1982) J. Exp. Med. 155, 1133-1147), which reacted with G(D3). R24 was found to bind weakly to G(D3) lactone I, but not to G(D3) lactone II. The results suggest that the monoclonal antibody requires both sialic acid residues for high affinity binding, and the complete lactonization results in a loss of negative charges and/or a change in the overall conformation of the oligosaccharide moiety which may account for the loss of binding.

Original languageEnglish (US)
Pages (from-to)3478-3483
Number of pages6
JournalJournal of Biological Chemistry
Volume264
Issue number6
StatePublished - Jan 1 1989
Externally publishedYes

Fingerprint

Gangliosides
Lactones
Protons
Monoclonal Antibodies
Nuclear magnetic resonance
N-Acetylneuraminic Acid
Esters
DEAE-Dextran
Column chromatography
Oligosaccharides
Galactose
Chromatography
Magnetic Resonance Spectroscopy
Nuclear magnetic resonance spectroscopy
Conformations
lactone II
Temperature

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

High resolution proton NMR studies of gangliosides. Structure of two types of G(D3) lactones and their reactivity with monoclonal antibody R24. / Ando, S.; Yu, Robert K; Scarsdale, J. N.; Kusunoki, S.; Prestegard, J. H.

In: Journal of Biological Chemistry, Vol. 264, No. 6, 01.01.1989, p. 3478-3483.

Research output: Contribution to journalArticle

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abstract = "Gangioside G(D3) was converted at room temperature to two stable lactones, denoted as G(D3) lactones I and II. The reaction sequence was presumed to be G(D3) → G(D3) lactone I → G(D3) lactone II based on the time course of their production. Lactone I behaved as a monosialoganglioside and lactone II as a neutral species. The two lactones were isolated by DEAE-Sephadex column chromatography. The positions of the inner ester linkages were investigated by two-dimensional J-correlated proton NMR spectroscopy. An ester linkage was most likely formed between the carboxyl group of the external sialic acid residue and C9-OH of the internal sialic acid residue in lactone I. In addition to this ester linkage, a second ester linkage between the carboxyl group of the internal sialic acid and C2-OH of the galactose residue was likely formed in lactone II. The structural changes induced by lactonization were further examined by their reactivity with the monoclonal antibody R24 (Puckel, C.S., Lloyd, K.O., Travassos, L.R., Dippold, W.G., Oettgen, H.F., and Old, L.J. (1982) J. Exp. Med. 155, 1133-1147), which reacted with G(D3). R24 was found to bind weakly to G(D3) lactone I, but not to G(D3) lactone II. The results suggest that the monoclonal antibody requires both sialic acid residues for high affinity binding, and the complete lactonization results in a loss of negative charges and/or a change in the overall conformation of the oligosaccharide moiety which may account for the loss of binding.",
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