Conformational flexibility and dynamics of two (1→6)-linked disaccharides related to an oligosaccharide epitope expressed on malignant tumour cells
2009 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 15, no 35, 8886-8894 p.Article in journal (Refereed) Published
The conformational flexibility and dynamics of two (1→6)-linked disaccharides that are related to the action of the glycosyl transferase GnT-V have been investigated. NMR NOE and T-ROE spectroscopy experiments, conformation-dependent coupling constants and molecular dynamics (MD) simulations were used in the analyses. To facilitate these studies, the compounds were synthesised as α-d-[6-13C]-Manp-OMe derivatives, which reduced the 1H NMR spectral overlap and facilitated the determination of two- and three-bond 1H,1H, 1H,13C and 13C,13C-coupling constants. The population distribution for the glycosidic ω torsion angle in α-d-Manp-(1→6)-α-d-Manp-OMe for gt/gg/tg was equal to 45:50:5, whereas in α-d-Manp-OMe it was determined to be 56:36:8. The dynamic model that was generated for β-d-GlcpNAc-(1→6)-α-d-Manp-OMe by MD simulations employing the PARM22/SU01 CHARMM-based force field was in very good agreement with experimental observations. β-d-GlcpNAc-(1→6)-α-d-Manp-OMe is described by an equilibrium of populated states in which the ϕ torsion angle has the exo-anomeric conformation, the ψ torsion angle an extended antiperiplanar conformation and the ω torsion angle a distribution of populations predominantly between the gauche–trans and the gauche–gauche conformational states (i.e., gt/gg/tg) is equal to 60:35:5, respectively. The use of site-specific 13C labelling in these disaccharides leads to increased spectral dispersion, thereby making NMR spectroscopy based conformational analysis possible that otherwise might be difficult to attain.
Place, publisher, year, edition, pages
2009. Vol. 15, no 35, 8886-8894 p.
carbohydrates, enzymes, molecular dynamics, NMR spectroscopy, torsion angles
Research subject Organic Chemistry
IdentifiersURN: urn:nbn:se:su:diva-29504DOI: 10.1002/chem.200900507ISI: 000270045500030OAI: oai:DiVA.org:su-29504DiVA: diva2:233823