Preparation of heparin/heparan sulfate oligosaccharides with internal N-unsubstituted glucosamine residues for functional studies.

Abstract:

:The rare N-unsubstituted glucosamine (GlcNH (3)(+)) residues in heparan sulfate (HS) have important biological and pathophysiological roles. However, it is difficult to prepare naturally-occuring, GlcNH(3)(+)-containing oligosaccharides from HS because of their low abundance, as well as the inherent problems in both excising and identifying them. Therefore, the ability to chemically generate a series of structurally-defined oligosaccharides containing GlcNH(3)(+) residues would greatly contribute to investigating their natural role in HS. In this study, a series of heparin/HS oligosaccharides, from dp6 up to dp16 in length that possess internal GlcNH(3)(+) residues were prepared by a combination of chemical modification and heparinase I digestion. Purification and structural analysis of the major species derived from the octa- to dodeca-saccharide size fractions indicated the introduction of between 1 and 3 internal GlcNH(3)(+) residues per oligosaccharide. In addition, a GlcNH(3)(+) residue was selectively introduced into an internal position in a tetrasaccharide species by direct chemical modification. This selectivity has potential as an alternative procedure for preparing internally-modified oligosaccharides of various lengths. The utility of such oligosaccharides was demonstrated by a comparison of the binding of three different tetrasaccharide species containing 0, 1 and 2 free amino groups to the NK1 truncated variant of hepatocyte growth factor/scatter factor.

journal_name

Glycoconj J

journal_title

Glycoconjugate journal

authors

Wei Z,Deakin JA,Blaum BS,Uhrín D,Gallagher JT,Lyon M

doi

10.1007/s10719-011-9352-3

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

525-35

issue

8-9

eissn

0282-0080

issn

1573-4986

journal_volume

28

pub_type

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