Computational and NMR Conformational Analysis of Galactofuranoside Cycles Presented in Bacterial and Fungal Polysaccharide Antigens

Abstract

Unlike pyranoside cycles which are generally characterized by strictly defined conformational preferences, furanosides are flexible and may adopt a wide range of available conformations. During our previous studies, conformational changes of galactofuranoside cycles upon total sulfation were described computationally, using a simple Hartree–Fock (HF) method, and principal conformers of the 5-membered galactose ring were revealed. However, in the case of more complex disaccharide structures, it was found that this method and the widely applied DFT-B3LYP produced results that deviated from experimental evidence. In this study, other DFT functionals (PBE0 and double hybrid B2PLYP) along with RI-MP2 are employed to study the conformational behavior of the galactofuranoside ring. Reinvestigation of galactofuranosides with a lactic acid substituent at O-3 revealed that changes in the orientation of lactic acid residue at O-3 might induce conformational changes of the furanoside cycle. Such findings are important for further modeling of carbohydrate–protein interaction.

Conformational preferences of the flexible galactofuranose sugar in gas-phase

“…The case of furanosides is particularly daunting because any variation of the environment critically affects the conformation of the ring: Cocinero et al have reported 3 T 2 conformation for methyl β- d -ribofuranoside 21 whereas the methyl 2-deoxyribofuranoses in gas phase adopts 2 T 1 conformation (α-anomer) or 4 E/E 2 / 1 T 2 conformations (β-anomer). 22 Gerbst et al reported structures ranging from E O /E 2 to E 3 / 4 E for lactic acid- and propyl-galactofuranosides in solution; 12 Lowary et al highlighted the elusive character of βGal f OMe whereas the same conditions yielded conclusive 2 E data for αGal f OMe. 11 Strikingly, the later essentially adopts E 2 conformations in the gas phase, in contrast to the Southwest gas phase conformations previously reported for the N -acetylated galactofuranosides.…”

“…Gerbst et al reported alternative conformations of galactofuranoside derivatives using different DFT functionals and MP2 approaches. 12…”

“…Gerbst et al reported alternative conformations of galactofuranoside derivatives using different DFT functionals and MP2 approaches. 12 Gas phase spectroscopy in combination with quantum calculations constitutes an alternative approach, where the absence of environment conveniently allows examining the intrinsic conformational properties driven by intramolecular H-bonds networks; or even to investigate the influence of micro-environment (one solvent molecule, a charge. .…”