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J. Biol. Chem., Vol. 269, Issue 15, 11208-11215, 04, 1994
M Lyon, JA Deakin and JT Gallagher
The structure of rat liver heparan sulfate (HS) has been investigated using
a combination of (a) chain scission with specific reagents, (b)
disaccharide compositional analysis, and (c) end-referenced sequence
analysis of the proximal, protein-linked region of the chain. This study
reveals that the liver synthesizes a highly sulfated HS species (1.34
sulfates/disaccharide), particularly high in N-sulfation (60%) and
2-O-sulfate content (36%). Approximately half of the latter is found in
trisulfated disaccharides, i.e. IdceA(2-OSO3) alpha 1-4GlcNSO3 (6-OSO3).
End-referencing methodology established the existence of an extended,
unmodified heparan (GlcUA beta 1-4GlcNAc) sequence, 8-11 disaccharides in
length, attached to the linkage tetrasaccharide, similar to that found in a
number of other HS species. Directly following this is a mixed
HexUA1-4GlcNR(6-OSO3) (where GlcNR represents alpha-D-glucosamine with an
unspecified N-substituent)-containing sequence of variable length,
culminating in the appearance of the first IdceA(2-OSO3) residue
approximately 20 disaccharides from the linkage region, i.e. approximately
40% along the length of the chain. The distal 60% of the polysaccharide is
highly sulfated (approximately 2 sulfates/disaccharide) and mainly
comprises three heparin-like domains, highly enriched in IdceA(2-OSO3)
residues. Overall, liver HS qualifies as an extreme member of the HS
family, with a considerable proportion of heparin-like structure
asymmetrically concentrated to the distal part of the chain.
Liver heparan sulfate structure. A novel molecular design
Cancer Research Campaign, Christie Hospital, Manchester, United Kingdom.
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