VANCOMYCIN - CONFORMATIONAL CONSEQUENCES OF THE SUGAR SUBSTITUENT

High-resolution, three-dimensional structures of vancomycin and aglyco -vancomycin in DMSO were determined by nuclear magnetic resonance, met ric matrix distance geometry, and molecular dynamics calculations. Con formational flexibility fast on the NMR time scale was examined by ens emble-based calculations which apply the experimentally derived restra ints as an ensemble average. Two families of conformations of vancomyc in, differing in the positioning of the vancosamine substituent, were observed. In contrast, the aglyco-vancomycin adopts only one conformat ion in solution. The conformations of vancomycin and the aglyco-vancom ycin differ in the alignment of the amide protons which participate in the hydrogen-bonding network with the cell-wall precursor and orienta tion of the aromatic rings relative to the backbone. Therefore, the hi gh-resolution structural characterization provides insight into a poss ible role of glycosylation on the activity of this important family of antibiotics.