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 Streeter, Gary S. Jacob

Research output: Contribution to journalArticle

69 Citations (Scopus)

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 1994
Externally publishedYes

Fingerprint

L-Selectin
galactoside 3-fucosyltransferase
Inhibitory Concentration 50
Inhibitor
Fucosyltransferases
Synthesis
Galactosyltransferases
Biochemistry
Disaccharides
Galactose
Sulfates
Ligands
Precursor
Receptor
Selectins
sulfated glycoprotein p50
trans-sialidase
Mm
Form

Keywords

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

ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Public Health, Environmental and Occupational Health
  • Neuropsychology and Physiological Psychology
  • Hematology
  • Biochemistry

Cite this

Enzymatic synthesis of a 6'-sulphated sialyl-lewis which is an inhibitor of L-selectin binding to peripheral addressin. / Scudder, Peter R.; Shailubhai, Kunwar; Duffin, Kevin L.; Streeter, Philip; Jacob, Gary S.

In: Glycobiology, Vol. 4, No. 6, 12.1994, p. 929-932.

Research output: Contribution to journalArticle

Scudder, Peter R. ; Shailubhai, Kunwar ; Duffin, Kevin L. ; Streeter, Philip ; Jacob, Gary S. / Enzymatic synthesis of a 6'-sulphated sialyl-lewis which is an inhibitor of L-selectin binding to peripheral addressin. In: Glycobiology. 1994 ; Vol. 4, No. 6. pp. 929-932.
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AB - 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.

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