Conformational Dynamics of a Central Trisaccharide Fragment of the LeaLex Tumor Associated Antigen Studied by NMR Spectroscopy and Molecular Dynamics Simulations
2012 (English)In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, no 25, 4705-4715 p.Article in journal (Refereed) Published
Certain carbohydrate structures are recognized as cancer antigens, and identification of these and relevant epitopes are essential in fighting the disease. The trisaccharide beta-D-GlcpNAc-(1?3)-beta-D-Galp-(1?4)-beta-D-GlcpNAc-OMe represents a model for the central region of the LeaLex hexasaccharide and it has herein been investigated by 1D 1H,1H-NOESY experiments to obtain effective interresidue protonproton distances as well as by 2D J-HMBC experiments to determine transglycosidic 3JCH coupling constants. Molecular dynamics (MD) simulations using explicit water as solvent and three different carbohydrate force fields, namely, GLYCAM06, PARM22/SU01, and CHARMM2011, were employed for the interpretation of experimental data. Overall, the force field based MD simulations are able to reproduce the experimental data and the ? torsion angle at the beta-(1?3)-linkage is concluded to be flexible. In addition, different minor states were present for the three force fields with either anti-? or non-exo-anomeric conformations. Transitions between the exo-anomeric and the non-exo-anomeric conformations for the f torsion angle at the beta-(1?4)-linkage in one of the MD simulations were analyzed in detail. It was found that hydrogen-bonding water molecules, interresidue hydrogen bonds and the transitions between antiperiplanar and synperiplanar conformations for the tH torsion angle of an N-acetyl group were all essential in the description of the glycosidic transition process. In particular, the transition of tH may be a general way of regulating other transitions into less populated but biologically important conformational regions.
Place, publisher, year, edition, pages
2012. no 25, 4705-4715 p.
Carbohydrates, Conformation analysis, NMR spectroscopy, Molecular dynamics
Research subject Organic Chemistry
IdentifiersURN: urn:nbn:se:su:diva-81235DOI: 10.1002/ejoc.201200569ISI: 000307937800008OAI: oai:DiVA.org:su-81235DiVA: diva2:561431
FunderSwedish Research CouncilKnut and Alice Wallenberg Foundation