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 C-4(1) chair conformation, the native 2-N-acetyl-4-amino Gal24N exhibits conformational mobility with comparable populations in the C-4(1) chair and S-5(1) skew conformations, as determined using MD simulation for the partial trisaccharide Me-beta-D-Glc6P-(1 --> 3)-alpha-D-Gal24N-[6-PC]-(1 --> 4)-alpha-D-GalNAc and from the intra-ring NOE effects. P-31-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)-beta-D-Glc6P]. Molecular modelling and MD simulation experiments confirmed that such an interaction was feasible with the Gal24N galactopyranose ring in the inverted B-1,B-4 or skew S-5(1) conformation.