title: Three-dimensional structure of cyclic antibiotic teicoplanin aglycone using NMR distance and dihedral angle restraints in a DMSO solvation model.
abstract: The three-dimensional solution conformation of teicoplanin aglycone was determined using NMR spectroscopy. A combination of NOE and dihedral angle restraints in a DMSO solvation model was used to calculate an ensemble of structures having a root mean square deviation of 0.17 Å. The structures were generated using systematic searches of conformational space for optimal satisfaction of distance and dihedral angle restraints. Comparison of the NMR-derived structure of teicoplanin aglycone with the X-ray structure of a teicoplanin aglycone analog revealed a common backbone conformation with deviation of two aromatic side chain substituents. Experimentally determined backbone (13)C chemical shifts showed good agreement with those computed at the density functional level of theory, providing a cross validation of the backbone conformation. The flexible portion of the molecule was consistent with the region that changes conformation to accommodate protein binding. The results showed that a hydrogen-bonded DMSO molecule in combination with NMR-derived restraints together enabled calculation of structures that satisfied experimental data.
authors.affiliation: Materials and Analytical Sciences, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: Nina C
authors.initials: NC
authors.lastname: Gonnella
authors.affiliation: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: Nelu
authors.initials: N
authors.lastname: Grinberg
authors.affiliation: Materials and Analytical Sciences, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Mcloughlin
authors.affiliation: Materials and Analytical Sciences, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.|Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: Om
authors.initials: O
authors.lastname: Choudhary
authors.affiliation: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Fandrick
authors.affiliation: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: Shengli
authors.initials: S
authors.lastname: Ma
mesh_terms: D003198:Computer Simulation; D004121:Dimethyl Sulfoxide / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D012996:Solutions; D017334:Teicoplanin / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D012996:Solutions; D017334:Teicoplanin; C063101:teicoplanin aglycone; D004121:Dimethyl Sulfoxide
keywords: 3D structure; conformation; density functional theory; nuclear magnetic resonance; solvation model; teicoplanin aglycone