GLUCOSIDASE INHIBITORS - STRUCTURES OF DEOXYNOJIRIMYCIN AND CASTANOSPERMINE

High-resolution structures of the glucosidase inhibitors deoxynojirimy cin (dNM) and castanospermine (CAST) have been determined by X-ray dif fraction. The crystal parameters are a = 10.751(3) and 8.788(3) Angstr om, b = 9.263(3) and 8.172(3) Angstrom, c = 7.719(2) and 6.507(2) Angs trom, and space group P2(1)2(1)2(1) and P2(1) for dNM and CAST, respec tively. (beta = 105.44(8)degrees for CAST.) The absolute configuration of CAST has also been established. Stereochemical comparisons with na tural glucosidase substrates such as maltose and methyl glucoside show great similarities in the positioning of functional groups, and indic ate the basis for enzyme inhibition. Conformational comparison between dNM and CAST suggests the greater activity of CAST may be due to the fixed axial positioning of the 06 atom; the results have implications for the design of analogues for potential anti-HIV and other antiviral therapies.