Solution structure analysis of oligosaccharides by NMR and molecular mechanics
Description
Nuclear magnetic resonance spectroscopy and computational methods were applied to the elucidation of solution structure of some fructans. A rigid compound, gibberellic acid, was studied by both NMR and a variety of computational methods to find suitable computational methods for the molecular modeling. MMX in PCMODEL gave the best correlation in torsion angles with those from X-ray diffraction data among the tested methods (MMX in PCMODEL, AM1, MNDO, MINDO/3 in MOPAC). $\sp3J\sb{\rm C-H}$ information from NMR experiment showed good correlation with torsion angles from MMX optimized structure. This indicated that data obtained from NMR spectroscopy could be used together with molecular modeling results to give a good picture of a molecule NMR spectral assignments of 6-kestose and neokestose were carried out by various two dimensional techniques. $\sp3J\sb{\rm C-H}$ coupling NOESY data were used to differentiate the two fructose units in neokestose and 6-kestose, respectively. Levanbiose and $\beta$- scD-fructofuranosyl-(2$\to$6)-$\beta$- scD-glucopyranoside were studied by molecular mechanics (MM2-87) with the flexible modeling method. The N-H study of extended oligomers from dimers indicated that the lowest energy dimers were not suitable for polymer structures although some of the dimers with moderate energies were To study larger carbohydrates, flexible method used here is impractical considering the computing time requirements. Standard rigid-residue methods will not properly model fructans. A new method was proposed and tested on a fructan tetramer. Starting from flexible modeling of the constituent trimers, a library of conformer files was created. Each file contains information on one constituent ring with specific adjacent residues of the target tetramer. By combining the different rings together from this library, a series of oligomer structures with different linkage angle combinations were constructed. The initial steric energies of these structures were calculated to screen for low energy structures. These would then be used for searching energy minima. The results were compared with the standard rigid rotation method and flexible modeling. Two FORTRAN programs, DBCREATE and OLIGOGEN, were written to extract monomers from flexible study for the library files, and to build the structure of the oligomer under analysis