CONFORMATIONAL PROPERTIES OF A CYCLIC OLIGOSACCHARIDE - PHA-D-GLUCOPYRANOSYL-(1-]4)-BETA-D-GLUCOPYRANOSYL]

The title compound is a cyclic oligosaccharide having six glucopyranos e residues linked alternatively by alpha-(1 --> 4) and beta-(1 --> 6) glycosidic linkages. Like cyclodextrin analogues it is expected to exh ibit an internal cavity and to form inclusion complexes with other spe cies. In order to investigate its conformational preferences, an exten sive conformational search was carried out using a combination of Metr opolis Monte-Carlo (MMC) procedure in the glycosidic torsion angle spa ce 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. Full y minimized conformations were gathered into families using a clusteri ng technique based on RMS fitting over the glycosidic torsion angle va lues. A wide range of local energy minima were identified in spite of ring closure conditions that constrained the structure of the oligosac charide. Low energy conformers were stabilized by intramolecular inter actions between distant residues. From the Bolzmann population of the best structures derived from the clustering results, various average p roperties were calculated and compared with experimental data obtained by high resolution NMR. Interpretation of these experimental values ( heteronuclear coupling constants, rotating frame nuclear Overhauser ef fects, relaxation times) relies on the use of Karplus like equations ( coupling constants) and analysis of the full relaxation rate matrix tr eatment (ROE). The quality of the molecular modelling strategy used is assessed by the agreement obtained between calculated and measured ob servables.