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Combined NMR and molecular modeling study of an iduronic acid-containing trisaccharide related to antithrombotic heparin fragments.
- Source :
-
Bioorganic & medicinal chemistry [Bioorg Med Chem] 1997 Jul; Vol. 5 (7), pp. 1301-9. - Publication Year :
- 1997
-
Abstract
- An iduronic acid-containing trisaccharide, methyl-O-(4-O-methyl-2,3,6-tri-O-sulfo-alpha-D-glucopyranosyl-(1-->4)-O- (2-O-sulfo-alpha-L-idopyranosyluronic acid)-(1-->4)-O-2,6-di-O-sulfo-alpha-D-glucopyranoside, related to antithrombotic heparin fragments has been subjected to a combined NMR and molecular modeling investigation. The conformational behavior of the two constituting disaccharide segments was investigated using a systematic grid search approach with the MM3 force field along with the proper parameters for the sulfate ester group. The exploration of the potential energy surfaces of the trisaccharide was performed through the use of the CICADA methods interfaced with the MM3 force field. In all cases, the 2-O-sulfo-alpha-L-iduronate moiety was given the three favored ring conformations (1)C4, (4)C1, and (2)S0. Conformations were clustered into families, four of which are likely to exhibit significant occupancy in solution. The different low-energy conformational families display different orientations at the glycosidic linkages and/or different ring shapes for the iduronate ring. The (2)S0 conformation is the major one for the 2-O-sulfo-alpha-L-iduronate but is still in equilibrium with the (1)C4 ring shape. The occurrence of such a conformational equilibrium in solution was probed via high-resolution NMR spectroscopy through measurements of coupling constants and NOE build-up. These results are in keeping with the observation that 2-O-sulfated pentasaccharides display a similar affinity for antithrombin III as their 2-N-sulfated counterparts.
- Subjects :
- Angiotensin III chemistry
Angiotensin III metabolism
Binding Sites
Carbohydrate Conformation
Carbohydrate Sequence
Chemical Phenomena
Chemistry, Physical
Fibrinolytic Agents metabolism
Heparin metabolism
Iduronic Acid metabolism
Magnetic Resonance Spectroscopy methods
Molecular Sequence Data
Sulfates chemistry
Sulfates metabolism
Thermodynamics
Trisaccharides metabolism
Fibrinolytic Agents chemistry
Heparin chemistry
Iduronic Acid chemistry
Models, Molecular
Trisaccharides chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 0968-0896
- Volume :
- 5
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 9377090
- Full Text :
- https://doi.org/10.1016/s0968-0896(97)00087-4