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The effect of variations in substitution on the conformation of
iduronate-containing sequences in heparin and heparan sulphate has been studied
using a series of chemically-modified heparins in which substitution with O- and
N-sulphate and N-acetyl substituents has been systematically altered.
Monosaccharides corresponding to residues in these modified heparins have also
been investigated. The conformations of the glycosidic linkages in O- and
N-desulphated re-N-acetylated heparin, O-desulphated re-N-sulphated heparin, and
6-O-desulphated re-N-sulphated heparin have been compared with those of
N-desulphated re-N-acetylated heparin and of heparin itself, which have been
compared with those of N-desulphated re-N-acetylated heparin and of heparin
itself, which have previously been reported [B. Mulloy, M.J. Forster, C. Jones,
and D.B. Davies, Biochem. J., 293 (1993) 849-858]. The overall conformation of
all the polysaccharides is shown to be similar, regardless of substitution
pattern. The conformational equilibrium of the pyranose ring of iduronic acid
residues in the polysaccharides has been monitored by the use of 13C NMR
chemical shift temperature coefficients, and shown to be similar for all the
modified heparins with the exception of N-desulphated re-N-acetylated heparin.
Circular dichroism spectra of all the polysaccharides are reported, and their
variations attributed to differences in the proportions of pyranose ring forms
in the iduronate conformational equilibrium.
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