Structural Analysis of Carbohydrates by Nuclear Magnetic Resonance Spectroscopy and Molecular Simulations: Application to Human Milk Oligosaccharides

Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields

“…However, the one-bond heteronuclear coupling constant 1 J C1′,H1′ in M4M deviates, for which the experimental value of 1 J C1′,H1′ = 171.8 Hz; a comparison to M2M having 1 J C1′,H1′ = 171.2 Hz and M3M with 1 J C1′,H1′ = 171.8 Hz 58 shows that these one-bond coupling constants are comparable, indicating a similar conformational preference for the ϕ torsion angle in the three disaccharides. In a previous study on the pentasaccharide LNF-1 103,104 a one-bond Karplus-type relationship for β-linked hexopyranosides facilitated the identification of the preferred exo-anomeric conformational region for the ϕ torsion angle, consistent with complementary experimental NMR data. The one-bond Karplus-type relationship for α-linked hexopyranosides, having a span of ∼8 Hz (eqn 1), was utilized in the analysis of the MD simulations that resulted in a deviation of the computed 1 J C1′,H1′ value (Table 2) to the experimentally determined one for both the CHARMM36 and Drude FFs.…”

Structure and function of non-digestible carbohydrates in the gut microbiome

“…A GC-MS method has been developed for the identification and quantification of 2'-FL and 3-FL in human milk as TMS-oxime derivatives (Balogh et al, 2015), whilst the application of NMR spectroscopy to structural analysis of HMO and other carbohydrates have been covered in depth by Maliniak and Widmalm (2014). Finally, an approach, based on the combined use of IMMS and welldefined oligosaccharide standards, has been successful to determine the exact positions of fucosyl residues in structurally complex glycans, such as sialosyl-fucosyl oligo-N-acetyllactosamine derivatives, which is relevant for HMO analysis (Sastre Toraño et al, 2019).…”

“…Lastly, some enlightening and comprehensive information has become available from the structural analysis of HMO by NMR and molecular simulations (Gu et al, 2021;Maliniak and Widmalm, 2014;Van Leeuwen et al, 2014. For further information, critical reviews on HMO analysis evaluating the advantages and limitations of these techniques have been published during the last years as those of Auer et al (2021) andvan Leeuwen (2019).…”

Parallel NMR Supersequences: Ten Spectra in a Single Measurement

“…Likewise, the COSY and HSQC-COSY modules can be replaced with the corresponding CLIP (clean in-phase) versions (Figures S2, S3, S5−S7, S10, and S11). 19,22 The five 2D NMR spectra recorded in a single p-NOAH-5 (BS C S J T/S) experiment (see Figure 2) contain optimal information for input to CASPER 11,20 21 the N-acetyl-D-glucosamine, methyl D-glucoside, and two D-galactose units were entered as sugar components into CASPER together with NMR data but linkage positions were given as wild cards; i.e., no information on the linkages, anomeric configurations, or sequences between sugar residues was given.…”

“…Particularly important are the TOCSY correlations with the anomeric protons and the three-bond HMBC correlations which reveal the trans-glycosidic connectivities. In the analysis of the tetrasaccharide β- d -Gal p -(1→4)-β- d -Glc p NAc-(1→3)-β- d -Gal p -(1→4)- d -Glc p -OMe (βLNnTOMe), the methyl glycoside of a human milk oligosaccharide, the N -acetyl- d -glucosamine, methyl d -glucoside, and two d -galactose units were entered as sugar components into CASPER together with NMR data but linkage positions were given as wild cards; i.e., no information on the linkages, anomeric configurations, or sequences between sugar residues was given.…”