Conformational Selection of Glycomimetics at Enzyme Catalytic Sites: Experimental Demonstration of the Binding of Distinct High-Energy Distorted Conformations of <i>C</i>-, <i>S</i>-, and <i>O</i>-Glycosides by <i>E. </i><i>C</i><i>oli</i> β-Galactosidases

Abstract

We show that the conformational features of the molecular complexes of E. coli beta-galactosidase and O-glycosides may differ from those formed with closely related compounds in their chemical nature, such as C- and S-glycosyl analogues. In the particular case presented here, NMR and ab initio quantum mechanical results show that the 3D-shapes of the ligand/inhibitor within the enzyme binding site depend on the chemical nature of the compounds. In fact, they depend on the relative size of the stereoelectronic barriers for chair deformation or for rotation around Phi glycosidic linkage.