Enzymatic synthesis of a 6'-sulphated sialyl-lewis which is an inhibitor of L-selectin binding to peripheral addressin

Peter R. Scudder, Kunwar Shailubhai, Kevin L. Duffin, Philip R. Streeter, Gary S. Jacob

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Abstract

A sulphated form of sialyl-Lewisx, NeuAcα2-3Galβ1-4(Fucα1-3)GlcNAc6OSO3β1-3Gal, was synthesized enzymatically from a precursor disaccharide, GlcNAc6OSO3β1-3Gal, using sequential steps involving β1,4-galactosyltransferase, α2,3-trans-sialidase and recombinant α1,3-fucosyltransferase, respectively. Successful enzymatic fucosylation at the 3 position of the GlcNAc6OSO3 residue demonstrated that fucosyltransferases are capable of generating, in situ, sulphated sialyl Lewisx structures containing sulphate at the 6 position of GlcNAc. The sulphated sialyl-Lewisx pentasaccharide produced by this procedure inhibited binding of a soluble form of L-selectin to 35SO4-labelled peripheral addressin with an IC50 of 0.8 mM, whereas sialyl-Lewisx tetrasaccharide was a weaker inhibitor, displaying an IC50 of 3.2 mM. Hemmerich and Rosen (Biochemistry, 33, 4820-4829, 1994) recently reported the presence of Galβ1-4GlcNAcO6SO3 structures on murine peripheral addressin Sgp50, in addition to sialyl Lewisx structures sulphated at the 6-O-galactose position. Based on our data, we suggest that sialyl Lewisx sulphated at the 6-O-GlcNAc position may also exist on receptors and function as a ligand for L-selectin.

Original languageEnglish (US)
Pages (from-to)929-932
Number of pages4
JournalGlycobiology
Volume4
Issue number6
DOIs
StatePublished - Dec 1 1994

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Keywords

  • Homing receptor
  • L-selectin
  • Lymphocyte
  • Peripheral addressin
  • Sulphated sialyl-Lewisx

ASJC Scopus subject areas

  • Biochemistry

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