Conformational properties of a cycle oligosaccharide: cyclotrikis-(1-->6)-[alphaD-glucopyranosyl-(1-->4)-beta-D-glucopyranosy l].

The title compound is a cyclic oligosaccharide having six glucopyranose residues linked alternatively by alpha-(1-->4) and beta-(1-->6) glycosidic linkages. Like cyclodextrin analogues it is expected to exhibit an internal cavity and to form inclusion complexes with other species. In order to investigate its conformational preferences, an extensive conformational search was carried out using a combination of Metropolis Monte-Carlo (MMC) procedure in the glycosidic torsion angle space and molecular mechanics procedures. To this end a specific program (METROCYCLIX) was developed. To reduce the MMC search, conformational maps of parent disaccharides were considered as starting entries. Fully minimized conformations were gathered into families using a clustering technique based on RMS fitting over the glycosidic torsion angle values. A wide range of local energy minima were identified in spite of ring closure conditions that constrained the structure of the oligosaccharide. Low energy conformers were stabilized by intramolecular interactions between distant residues. From the Bolzmann population of the best structures derived from the clustering results, various average properties were calculated and compared with experimental data obtained by high resolution NMR. Interpretation of these experimental values (heteronuclear coupling constants, rotating frame nuclear Overhauser effects, relaxation times) relies on the use of Karplus like equations (coupling constants) and analysis of the full relaxation rate matrix treatment (ROE). The quality of the molecular modelling strategy used is assessed by the agreement obtained between calculated and measured observables.