In solution oligosaccharides

The conformational behaviour in solution of a dermatan-derived tetra-saccharide has been explored by means of NMR spectroscopy, especially by NOE-based conformational analysis. RDCs were also measured for the tetrasaccharide in a phage solution and interpreted in combination with restrained MD simulations. 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 behaviour of the oligosaccharides in solution, which show a moderate flexibility at the central glycosidic linkage. Differences in the shapes of the different species with the IdoA in skew and in chair conformations and in the distribution of the sulphate groups were also highlighted.28... 

Fig. 3—Possible solution conformers of oligosaccharide sequences related to the Le and Leb antigens (Lea,Lex, sialyl Le", sialyl Lex, ALeb, ALey). As described in the text, oligosaccharides in solution sample 3D space in local energy-minima wells, so that the conformations shown are approximate only. The models stand only to show the stereochemical hindrance to movement in these branched oligosaccharides. The molecules are shown without the anomeric hydroxyl group. 

A coirplete understanding of the role of carbohydrates in biological systems requires knowledge of the distribution at equilibrium of the various conformers in aqueous solution. The conformational behavior of carbohydrates in solution can be examined from different vantage points (1,), but the most relevant approach is, no doubt, study of dilute solutions themselves. At present, high resolution NMR spectroscopy is the primary tool for determination of three-dimensional structure of oligosaccharides in solution. Optical rotation is also very sensitive to conformation (2) and there is a new, semi-enqpirical theory of optical rotation of oligosaccharides ( ). 

Conformational analysis of oligosaccharides in solution by NMR is mainly based on hydrogen-hydrogen distance information obtained from the nuclear Overhauser effect (n.O.e.) ( ). Other independent NMR... 

Until now, the determination of three-dimensional structures of oligosaccharides in solution was based primarily on proton-proton distance information obtained from n.O.e. data. Here, we discuss the application of three-bond proton-carbon coupling constants. 

NMR spectroscopy has developed during the last few years into a very powerful method to establish both the conformation of an oligosaccharide in solution and in the crystalline state. The solution conformation of a saccharide can be determined generally by the combination of 13C-NMR and H-NMR techniques. 2-d methods became available in the last few years and are prerequisites for the elucidation of the three dimensional structure of an oligosaccharide [7]. Both NOE measurements [21] as well as traditional determination of coupling constants and chemical shifts are important tools for the determination of preferred conformations. 2-dimensional methods have greatly improved the accessibility of these parameters from complex molecules. 

E. De Clercq Antiviral activity of 5-substituted pyrimidine nucleoside analogues K. Bock The preferred conformation of oligosaccharides in solution inferred from high resolution NMR data and hard-sphere exo-anomeric calculations... 

The specific correlations of functional groups with the chemical shifts of carbon and associated protons are always important tools for structure elucidation of simple sugars as well as complex oligosaccharides. The conformational behavior [65,66] of a particular disaccharide and oligosaccharide in solution is determined not only by intramolecular interactions but also by potential interactions that exist between the oligosaccharide and its environment. In particular, the nature of the solvent or more generally the environment in which the compound finds itself, can profoundly affect its geometry. Two such important factors, namely the fully solvated state (i. e. the molecule free in solution) and the molecule solvated by a macromolecular receptor (i. e. the molecule bound to the active site of the protein) contribute to the preferred conformation. 

The most significant advantage offered by macromolecular force fields, such as AMBER,108.109 CHARMm,no and GROMOS,iii.n2 over those already discussed is suitability for performing MD simulations. This feature, when combined with the option to treat solvent explicitly under periodic boundary conditions, leads to a realistic approach to simulating the properties of the oligosaccharides in solution. Moreover, physical observables such as solvent RDFs may be used as criteria to determine the accuracy of the treatment... 

K. Bock, Pure Appl. Chem., 55, 605 (1983). The Preferred Conformation of Oligosaccharides in Solution Inferred from High Resolution NMR Data and Hard Sphere Exo-Anomeric Calculations. 

A complete structural determination of chitin/chitosan, subsequent to its isolation and purification, involves the determination (the constituent of the two monosaccharides the molecular size the molecular size distribution the linkage positions between the monomer units their sequence and degree of heterogeneity and any preferred conformation of the molecule(s) present). NMR spectroscopy can be used for structural characterization and conformational analysis of oligosaccharides in solution (van Halbeek 1996, Chaplin 2000). Conformational changes accompanied with metal-binding were examined by means of C NMR spectroscopy (Saito et al. 1987a,b). 

Reviews have been published on progress over the last 20 years in computional methods for studying oligo- and poly-saccharide conformations in the solid state and in solution, and on the newer techniques of H-n.m.r. spectroscopy which have proved useful in the elucidation of oligosaccharide structures. A review and a symposium report have appeared on the conformational analysis of oligosaccharides in solution by n.m.r. methods combined with... 

These subtle geometry changes are of little consequence to the overall conformation of an oligosaccharide in. solution, except in so far as they may lead to more or less puckered pyranoid rings. In biomolecular force fields this bond-torsion coupling may be reproduced crudely by employing... 

Homans SW (1993) Conformation and dynamics of oligosaccharides in solution. Glycobiology, 3 551-555. 

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