Conformations in Solution of alpha,alpha-Trehalose, alpha-d-Glucopyranosyl alpha-d-Mannopyranoside, and Their 1-Thioglycosyl Analogs, and a Tentative Correlation of Their Behaviour with Respect to the Enzyme Trehalase

Abstract

The conformation in solution of .alpha.-D-glucopyranosyl .alpha.-D-glucopyranoside (.alpha.,.alpha.-trehalose, 1), .alpha.-D-glucopyranosyl .alpha.-D-mannopyranoside (3) and their corresponding 1-thioglycosyl analogs, .alpha.-D-glucopyranosyl 1-thio-.alpha.-D-glucopyranoside (1-thio-.alpha.,.alpha.-trehalose, 2) and .alpha.-D-glucopyranosyl 1-thio-.alpha.-D-mannopyranoside (4) were established from high-resolution 1H-NMR and 13C-NMR measurements. These experimental results are in good agreement with the conformations as inferred from hard-sphere calculations. The dihedral angles .vphi.H and .psi.H are not significantly different for the O-glycosyl disaccharides 1 and 3 compared with their 1-thioglycosyl analogs 2 and 4; however, the internuclear H-1-H-1'' and H-1-H-5'' distances appear to be longer for 1-thiodisaccharides. This may account for the differences in affinities of cockchafer (Melolontha vulgaris) trehalase which have been observed. This enzyme exhibits less affinity for the competitive inhibitor .alpha.-D-glucopyranosyl 1-thio-.alpha.-D-mannopyranoside (4) than for its O-glycosyl analog 3 (Ki 0.055 mM vs. 0.0057 mM). From the similarity in Ki between 1-thio-.alpha.,.alpha.-trehalose and .alpha.-D-glucopyranosyl 1-thio-.alpha.-D-mannopyranoside (0.050 mM vs. 0.055 mM), it is possible to assume a similar decrease in the enzyme affinity between the natural substrate (1) and the corresponding 1-thioglycosyl inhibitor (2), which can together be ascribed to the aforementioned difference in the conformation of the molecules.