Conformational analysis of synthetic heparin‐like oligosaccharides containing α‐L‐idopyranosyluronic acid

C. A.A. van Boeckel*, S. F. van Aelst, G. N. Wagenaars, J. ‐R Mellema, H. Paulsen, T. Peters, A. Pollex, V. Sinnwell

*Corresponding author for this work
75 Citations (Scopus)


High‐field NMR spectroscopy of synthetic heparin‐like di‐ and trisaccharides has afforded a complete set of inter‐proton‐coupling data on α‐L‐idopyranosyluronic acid, which have been used for conformational analysis. These data lead to the conclusion that α‐L‐iduronic acid may display considerable conformational freedom including 1C4, 4C1 and 2S0 (e.g. compound 1) conformers. The 2‐O‐sulphate substituent at iduronic acid tends to stabilize the 1C4 conformation (e.g. compounds 2 and 4). In addition carbohydrate substituents at position 4 hinder the 4C1 conformation (e.g. compound 3a,b versus 1). Furthermore, the conformation of α‐L‐idopyranosyluronic acid 2‐sulphate is affected seriously by the substituent at position 2 of the non‐reducing glucosamine residue. Thus the presence of an ammonium group (i.e. compound 7) leads to unexpected deformation of the 1C4 form of iduronic acid, whereas a sulphamino substituent at this position (e.g. compound 5a,b) brings about the 2S0 skew boat conformation. The iduronic acid moiety of a trisaccharide (compound 6), which represents a part of the anti‐thrombin III‐binding site of heparin, shows conformational preference for the 2S0 form in aqueous solution under low ionic conditions. However, increasing the ionic strength (e.g. 3 M NaCl) causes the conformational equilibrium to incline towards the 1C4 chair conformer. This feature may be indicative for the mechanism of conformational control as exerted by the AT‐III protein upon heparin binding. Several molecular models of preferred conformers have been constructed; Nuclear Overhauser Enhancement data, exo‐anomeric effect and Van der Waals interactions have been taken into account.

Original languageEnglish
JournalRecueil des Travaux Chimiques des Pays‐Bas
Issue number1
Pages (from-to)19-29
Number of pages11
Publication statusPublished - 1987


Dive into the research topics of 'Conformational analysis of synthetic heparin‐like oligosaccharides containing α‐L‐idopyranosyluronic acid'. Together they form a unique fingerprint.

Cite this