NMR Solution Conformation of Heparin-Derived Tetrasaccharide

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Authors
Mikhailov, Dmitri
Mayo, Kevin H.
Vlahov, Ioncho R.
Toida, Toshihiko
Pervin, Azra
Linhardt, Robert J.
Issue Date
1996-08-15
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Abstract
The solution conformation of the homogeneous, heparin-derived tetrasaccharide delta UA2S(1-->4)-alpha-D-GlcNpS6S(1-->4)-alpha-L-IdoAp2S (1-->4)-alpha-D-GlcNpS6S (residues A, B, C and D respectively, where IdoA is iduronic acid) has been investigated by using 1H- and 13C-NMR. Ring conformations have been defined by J-coupling constants and inter-proton nuclear Overhauser effects (NOEs), and the orientation of one ring with respect to the other has been defined by inter-ring NOEs. NOE-based conformational modelling has been done by using the iterative relaxation matrix approach (IRMA), restrained molecular dynamics simulations and energy minimization to refine structures and to distinguish between minor structural differences and equilibria between various ring forms. Both glucosamine residues B and D are in the 4C1 chair conformation. The 6-O-sulphate group is oriented in the gauche-trans configuration in the D ring, whereas in the B ring the gauche-gauche rotomer predominates. Uronate (A) and iduronate (C) residues are mostly represented by 1H2 and 2S0 twisted boat forms, respectively, with small deviations in expected coupling constants and NOEs suggesting minor contributions from other A and C ring conformations.
Description
Biochemical Journal, 318, 93-102
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Full Citation
NMR Solution Conformation of Heparin-Derived Tetrasaccharide, D. Mikhailov, K. Mayo, I. R. Vlahov, T.T. Toida, R.J. Linhardt, Biochemical Journal, 318, 93-102, 1996.
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2646021
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