Structure and Conformation Determinations of Saccharides and Peptides in Solution and in the Solid-State

The structural complexity and conformational flexibility of saccharides along with limited experimental and theoretical techniques has hindered structure and conformation determinations of this class of biomolecules as needed to understand their diverse functions found in biological system.

The lab-developed MA’AT program, aims to use the redundant experimental J-couplings and the DFT-calculated Karplus-like equations to unbiasedly model saccharide conformation in solution. Chapter 2 describes the MA’AT analysis to determine contexts effect on biologically related βGlcNAc-(1→2)-αMan linkage conformation in complex N-glycan. Chapter 3 describes the first MA’AT analysis to determine the conformational equilibrium of alanine dipeptide. The comparison of MA’AT analysis to the MD simulation results provided the direct experimental validation of the theoretical data.

In Chapter 4, the conformational dependencies of geminal 13C−13C J-couplings as a function of the exocyclic hydroxyl conformations in saccharides were explored and parameterized as DFT-calculated Karplus-like equations. A combined solid-state 13C NMR and X-ray crystallography experimental approach was used to validate the predicted behaviors using seven doubly 13C-labeled saccharide crystals in solid-state.

The fundamental structural properties of saccharides are investigated in solid-state using X-ray crystallography, as shown in Chapter 5 – 7. In Chapter 5, a solvomorphism phenomenon is reported, which was caused by the crystal transformation between the methyl β-lactoside monohydrate and methyl β-lactoside methanol solvate crystals. In Chapter 6, the ionic hydrogen bonding in saccharides is reported, which is based on the structural analysis of D-mannosamine hydrochloride and related α-D-glucosamine hydro-chloride, β-D-galactosamine hydrochloride crystals. Lastly, the topological and charge-density analysis of the oxygen lone pairs in five high-quality saccharide crystals (forty-seven oxygen atoms in two chemical bond types), and their implications for the hydrogen bonding (thirty-one hydrogen bonding) are reported in Chapter 7.