Glycan Stability and Flexibility: Thermodynamic and Kinetic Characterization of Nonconventional Hydrogen Bonding in Lewis Antigens.

Kwon J, Ruda A, Azurmendi HF, Zarb J, Battistel MD, Liao L, Asnani A, Auzanneau FI, Widmalm G, Freedberg DI

J. Am. Chem. Soc. 145 (18) 10022-10034 [2023-05-10; online 2023-04-26]

We provide evidence for CH-based nonconventional hydrogen bonds (H-bonds) for 10 Lewis antigens and two of their rhamnose analogues. We also characterize the thermodynamics and kinetics of the H-bonds in these molecules and present a plausible explanation for the presence of nonconventional H-bonds in Lewis antigens. Using an alternative method to simultaneously fit a series of temperature-dependent fast exchange nuclear magnetic resonance (NMR) spectra, we determined that the H-bonded conformation is favored by ∼1 kcal/mol over the non-H-bonded conformation. Additionally, a comparison of temperature-dependent 13C linewidths in various Lewis antigens and the two rhamnose analogues reveals H-bonds between the carbonyl oxygen of the N-acetyl group of N-acetylglucosamine and the OH2 group of galactose/fucose. The data presented herein provide insight into the contribution of nonconventional H-bonding to molecular structure and could therefore be used for the rational design of therapeutics.

Swedish NMR Centre (SNC) [Service]

PubMed 37099481

DOI 10.1021/jacs.2c13104

Crossref 10.1021/jacs.2c13104

pmc: PMC10176581

Publications 9.5.0