Conformational Analysis of a Dermatan Sulfate - Derived Tetrasaccharide by NMR, Molecular Modeling and Residual Dipolar Couplings
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Authors
Silipo, A.
Zhang, Z.
Cañada, F.J.
Molinaro, A.
Linhardt, Robert J.
Jiménez-Barbero, J.
Issue Date
2008-01-25
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
The solution conformation behavior of a dermatan-derived tetrasaccharide--Delta HexA-(1-->3)-GalNAc4S-beta-(1-->4)-IdoA-alpha-(1-->3)-red-GalNAc4S (S is a sulfate group)--has been explored by means of NMR spectroscopy, especially by NOE-based conformational analysis. The tetrasaccharide was present as four species, two of which are chemically different in the anomeric orientation of the reducing 2-deoxy-2-acetamido-galactose (red-GalNAc) residue, while the other two are the result of different conformations of the iduronic acid (IdoA) unit. The two alpha-beta-interconverting anomers were present in a 0.6:1 ratio. Ring conformations have been defined by analysis of (3)J(H,H) coupling constants and interresidual NOE contacts. Both 2-deoxy-2-acetamido-galactose (GalNAc) residues were found in the (4)C(1) chair conformation, the unsaturated uronic acid (Delta-Hex A) adopts a strongly predominant half-chair (1)H(2) conformation, while the IdoA residue exists either in the (1)C(4) chair or in the (2)S(0) skewed boat geometries, in a 4:1 ratio. There is a moderate flexibility of Phi and Psi torsions as suggested by nuclear Overhauser effects (NOEs), molecular modeling (MM), and molecular dynamics (MD) studies. This was further investigated by residual dipolar couplings (RDCs). One-bond C--H RDCs ((1)D(C,H)) and long-range H-H ((3)D(H,H)) RDCs were measured for the tetrasaccharide in a phage solution and interpreted in combination with restrained MD simulation. The RDC-derived data substantially confirmed the validity of the conformer distribution resulting from the NOE-derived simulations, but allowed an improved definition of the conformational behavior of the oligosaccharides in solution. In summary, the data show a moderate flexibility of the four tetrasaccharide species at the central glycosidic linkage. Differences in the shapes of species with the IdoA in skew and in chair conformations and in the distribution of the sulfate groups have also been highlighted.
Description
ChemBiochem, 9, 240-252
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
Conformational Analysis of a Dermatan Sulfate - Derived Tetrasaccharide by NMR, Molecular Modeling and Residual Dipolar Couplings, A. Silipo, Z. Zhang, F. J. Cañada, A. Molinaro, R. J. Linhardt, J. Jiménez-Barbero, ChemBiochem, 9, 240-252, 2008.
Publisher
European Chemical Societies
Terms of Use
Journal
Volume
Issue
PubMed ID
DOI
ISSN
14397633
14394227
14394227