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  • Does Inter-Residue Hydrogen Bonding in β-(1→4)-Linked Disaccharides Influence Linkage Conformation in Aqueous Solution?
Title: Does Inter-Residue Hydrogen Bonding in β-(1→4)-Linked Disaccharides Influence Linkage Conformation in Aqueous Solution?
Two disaccharides, methyl β-d-galactopyranosyl-(1→4)-α-d-glucopyranoside (1) and methyl β-d-galactopyranosyl-(1→4)-3-deoxy-α-d-ribo-hexopyranoside (3), were prepared with selective 13C-enrichment to allow measurement of six trans-O-glycosidic J-couplings (2JCOC, 3JCOCH, and 3JCOCC) in each compound. Density functional theory (DFT) was used to parameterize Karplus-like equations that relate these J-couplings to either ϕ or ψ. MA’AT analysis was applied to both linkages to determine mean values of ϕ and ψ in each disaccharide and their associated circular standard deviations (CSDs). Results show that deoxygenation at C3 of 1 has little effect on both the mean values and librational motions of the linkage torsion angles. This finding implies that, if inter-residue hydrogen bonding between O3H and O5′ of 1 is present in aqueous solution and persistent, it plays little if any role in dictating preferred linkage conformation. Hydrogen bonding may lower the energy of the preferred linkage geometry but does not determine it to any appreciable extent. Aqueous 1-μs MD simulation supports this conclusion and also indicates greater conformational flexibility in deoxydisaccharide 3 in terms of sampling several, conformationally distinct, higher-energy conformers in solution. The populations of these latter conformers are low (3–14%) and could not be validated by MA’AT analysis. If the MD model is correct, however, C3 deoxygenation does enable conformational sampling over a wider range of ϕ/ψ values, but linkage conformation in the predominant conformer is essentially identical in both 1 and 3.  more » « less
Award ID(s):
2002628
PAR ID:
10496483
Author(s) / Creator(s):
; ; ; ; ;
Publisher / Repository:
ACS Publications
Date Published:
Journal Name:
The Journal of Physical Chemistry B
Volume:
128
Issue:
10
ISSN:
1520-6106
Page Range / eLocation ID:
2317 to 2325
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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