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 s ulfur in the nonreducing ring and either oxygen 1, sulfur 2 or selenium 3 a toms in the interglycosidic linkage is performed using high-quality NOE dat a for 1-3 and molecular mechanics calculations using the program PIMM91 for the derivatives 1 and 2. The compounds are substrate analogues of glucosid ases and inhibit glucoamylase 2. Theoretical NOE data, obtained from Boltzm ann averaging of potential energy maps from a grid search, are compared wit h the experimental data. The gross conformational features of all three com pounds 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 Psi from similar to - 30 degrees to similar to 180 degrees. Experimental N OE data and theoretical energy differences and population distributions sho w that the substitution of oxygen with sulfur or selenium results in an inc rease in the flexibility of the interglycosidic linkage in the latter compo unds. Thus, the population of the conformational family with a dihedral ang le Psi of similar to 180 degrees increases from similar to 1% (1) to simila r to 10% (2). (C) 1999 Elsevier Science Ltd. All rights reserved.