Molecular conformation, heparin

These conformer populations were confirmed by a number of n.O.e. measurements (the H2—H5 distance can act as a marker in identifying the ring form). The case of a hexasaccharide (compound 23 in Ref. 9) where the three IdoA residues yield different n.O.e. enhancements, is striking. Moreover, models computed with molecular mechanics have been put forward for the peculiar pentasaccharide of heparin. The models are in acceptable agreement with the observed vicinal coupling constants and n.O.e. values (10) (a full paper by Ragazzi, M. et al. Carbohvdr. Res.. is in press). 

The availability of synthetic and natural oligosaccharides and of advanced NMR methods lias contributed a deepened insight into the conformation of heparin/HS sequences in solution. While confirming the Ci(D) chair conformation for GlcA and GlcN residues, most of the studies have focused on the unique conformational properties of IdoA, as primarily deduced from widely different interproton coupling constants of this residue in different sequences. Combined NMR and molecular mechanics studies (reviewed in Refs. 195 and 196) have provided evidence that L-IdoA may be present in one of the three equienergetic conformations— C4, or — or in all three of these forms in rapid dynamic equi-... 

Figure 4. Schematic representation of interactions among thrombin, antithrombiin III (ATIII) and heparin (a) orpoly(vinyl sulfonate) (PVS) (b,c). The interaction is considered to depend on the steric position and continuity of sulfonate groups. TTie activity of PVS is less than that of heparin because of the difference of steric position of the sulfonate groups. On the other hand, the high molecular weight PVS (c) induces more conformational change of ATIII than the low molecular weight PVS (b) because of the continuity of the sulfonate groups.

Anslyn has prepared a heparin-selective sensor 118. Interaction with unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) causes conformational restriction of the arms of the receptor and a reduction in fluorescence intensity. The observed stability constant ( obs) for 118 was 1.4 X 10 for UFH in water at pH 7.4 (HEPES buffer). 

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