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NMR solution conformation of heparin-derived hexasaccharide
D Mikhailov1, R J Linhardt, K H Mayo
1Department of Biochemistry, University of Minnesota Health Science Center, 435 Delaware Street, S.E., Minneapolis, MN 55455, USA.
The Biochemical Journal
|January 10, 1998
Summary
Nuclear Magnetic Resonance (NMR) spectroscopy revealed the solution conformation of heparin-derived hexasaccharides. Specific sugar residues adopt distinct chair and boat forms, influencing overall oligosaccharide structure and stability.
Area of Science:
- Carbohydrate Chemistry
- Structural Biology
- Biophysical Chemistry
Background:
- Heparin's complex structure influences its biological activity.
- Understanding oligosaccharide conformation is crucial for structure-activity relationship studies.
Purpose of the Study:
- To elucidate the solution-state conformation of a homogeneous heparin-derived hexasaccharide.
- To characterize the intra-ring and inter-ring conformations of individual sugar residues.
Main Methods:
- 1H-NMR spectroscopy was employed to define intra-ring conformations using J-coupling constants and nuclear Overhauser effects (NOEs).
- NOE-based conformational modeling utilized the iterative relaxation matrix approach (IRMA) and restrained energy minimization.
- Molecular dynamics simulations in explicit solvent were used to assess conformational stability.
Main Results:
- Glucosamine residues (B, D, F) predominantly adopt the 4C1 chair conformation.
- The uronate residue (A) primarily exists in the 1H2 form, with minor contributions from the 2H1 form.
- Internal iduronate residues (C, E) exhibit an equilibrium between chair and skewed boat conformations.
Conclusions:
- The study provides detailed insights into the conformational heterogeneity of heparin-derived oligosaccharides.
- Conformational preferences of individual residues dictate the overall hexasaccharide structure.
- Refined structures were validated through molecular dynamics, confirming conformational stability.