MA’AT analysis has been applied to model conformational behaviors of 2-N-acetyl side-chains in several biologically important GlcNAc mono- and disaccharides. Density functional theory (DFT) was used to obtain parameterized equations that relate the magnitudes and signs of ten spin-coupling constants to model conformation about the C2–N2 bond. Six equations were used in conjunction with experimental values, obtained on selectively 13C-labeled compounds, to model the C1–C2–N2–CO torsion angle (θ1) in GlcNAc anomers. MA’AT analysis gave mean values of θ1 of ~100° for αGlcNAc and ~115° for βGlcNAc residues, with circular standard deviations (CSDs) of ~28°. A comparison of these results with those obtained by aqueous molecular dynamics (MD) simulation showed excellent agreement of mean values, but CSDs were consistently ~10° larger in MA’AT models of θ1 in βGlcNAc residues than in the MD models. Parameter space plots indicated unique single-state MA’AT fits of the data, and RMSDs were 0.3 Hz. The latter were two-fold smaller than the RMSDs back-calculated from MD models, indicating that the MA’AT models are better fits of the experimental spin-couplings. The conformational properties of N-acetyl and O-acetyl side-chains are very similar, and both O- and N-acetylation result in considerable rotational constraints on C–O or C–N bonds relative to the same bonds in unsubstituted parent compounds (i.e., free OH or NH2). The results show that MA’AT analysis can detect relatively small changes in mean torsion angles in solution that are consistent with those predicted by MD simulation, providing additional support for similar claims made from previous O-glycosidic linkage studies, and further validating the method as a powerful experimental technique complementary to MD simulation.

N-Acetyl side-chain conformation in saccharides: Characterization using redundant NMR spin-coupling constants and MA'AT analysis

ACS Spring 2022

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