Conformational analysis of maltoside heteroanalogues using high-quality NOE data and molecular mechanics calculations. Flexibility as a function of the interglycosidic chalcogen atom

The conformational analysis of three maltoside heteroanalogues containing sulfur in the nonreducing ring and either oxygen 1, sulfur 2 or selenium 3 atoms in the interglycosidic linkage is performed using high-quality NOE data for 1-3 and molecular mechanics calculations using the program PIMM91 for the derivatives 1 and 2. The compounds are substrate analogues of glucosidases and inhibit glucoamylase 2. Theoretical NOE data, obtained from Boltzmann averaging of potential energy maps from a grid search, are compared with the experimental data. The gross conformational features of all three compounds are similar in that they populate mainly two conformational regions of the potential energy maps. These two regions are equivalent to the ones found for maltose and interconvert through a rotation of the dihedral angle Ψ from ~-30°to ~180°. Experimental NOE data and theoretical energy differences and population distributions show that the substitution of oxygen with sulfur or selenium results in an increase in the flexibility of the interglycosidic linkage in the latter compounds. Thus, the population of the conformational family with a dihedral angle Ψ of ~180°increases from ~1% (1) to ~10% (2). Copyright (C) 1999 Elsevier Science Ltd.