Synthesis and conformational analysis of a pentasaccharide corresponding to the cell-wall polysaccharide of the Group A Streptococcus.
The synthesis and conformational analysis of a pentasaccharide corresponding to a fragment of the cell-wall polysaccharide (CWPS) of the bacteria Streptococcus Group A are described. The polysaccharide consists of alternating alpha-(1 --> 2)- and alpha-(1 --> 3)-linked L-rhamnopyranose (Rhap) residues with branching 2-acetamido-2-deoxy-D-glucopyranose (GlcpNAc) residues linked beta-(1 --> 3) to alternate rhamnose rings. The pentasaccharide is of interest as a possible terminal unit on the CWPS, for use in a vaccine. The syntheses employed a trichloroacetimidate glycosyl donor. Molecular dynamics (MD) calculations of the pentasaccharide with the force fields CVFF and PARM22, both in gas phase and with explicit water present, gave different predictions for the flexibility and preferred conformational space. Metropolis Monte Carlo (MMC) calculations with the HSEA force field were also performed. Experimental data were obtained from 1D transient NOE measurements. Complete build-up curves were compared to those obtained by full relaxation matrix calculations in order to derive a model of the conformation. Overall, the best fit between experimental and calculated data was obtained with MMC simulations using the HSEA force field. Molecular dynamics and MMC simulations of a tetrasaccharide corresponding to the Group A-variant polysaccharide, which differs in structure from Group A in lacking the GlcpNAc residues, were also performed for purposes of comparison.
Höög
Christer
C
Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada V5A 1S6.
Rotondo
Archimede
A
Johnston
Blair D
BD
Pinto
B Mario
BM
D001428:Bacterial Vaccines / Q000737:chemistry; D002236:Carbohydrate Conformation; D002473:Cell Wall / Q000737:chemistry; D003198:Computer Simulation; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009010:Monte Carlo Method; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000737:chemistry* / Q000276:immunology; D013291:Streptococcus / Q000737:chemistry*
D001428:Bacterial Vaccines; D009844:Oligosaccharides; D011135:Polysaccharides, Bacterial