The aqueous solution structure of a lipoteichoic acid from Streptococcus pneumoniae strain R6 containing 2,4-diamino-2,4,6-trideoxy-galactose: evidence for conformational mobility of the galactopyranose ring

The 2D-NOESY spectra for the per-N-acetylated and the native lipoteichoic acid (LTA) oligomer from Streptococcus pneumoniae strain R6 clearly indicate a difference in conformation of the 2,4,6-trideoxy-galactopyranose ring. Whereas the 2,4-N-acetylated Gal24N adopts the usual 4C1 chair conformation, the native 2-N-acetyl-4-amino Gal24N exhibits conformational mobility with comparable populations in the 4C1 chair and 5S1 skew conformations, as determined using MD simulation for the partial trisaccharide Me-β-d-Glc6P-(1 → 3)-α-d-Gal24N-[6-PC]-(1 → 4)-α-d-GalNAc and from the intra-ring NOE effects. 31P-NMR spectra point to a strong electrostatic or hydrogen-bonding interaction between the free 4-NH2 group on the Gal24N and the negatively charged diester phosphate group between adjacent pentasaccharide repeating-units [Ribitol-(5 → 6)-β-d-Glc6P]. Molecular modelling and MD simulation experiments confirmed that such an interaction was feasible with the Gal24N galactopyranose ring in the inverted B1,4 or skew 5S1 conformation.