Synthesis and Structural Analysis of Aspergillus fumigatus Galactosaminogalactans Featuring alpha-Galactose, alpha-Galactosamine and alpha-N-Acetyl Galactosamine Linkages

摘要

Galactosaminogalactan (GAG) is a prominent cell wall component of the opportunistic fungal pathogen Aspergillus fumigatus. GAG is a heteropolysaccharide composed of alpha-1,4-linked galactose, galactosamine and N-acetylgalactosamine residues. To enable biochemical studies, a library of GAG-fragments was constructed featuring specimens containing alpha-galactose-, alpha-galactosamine and alpha-N-acetyl galactosamine linkages. Key features of the synthetic strategy include the use of di-tert-butylsilylidene directed alpha-galactosylation methodology and regioselective benzoylation reactions using benzoyl-hydroxybenzotriazole (Bz-OBt). Structural analysis of the Gal, GalN and GalNAc oligomers by a combination of NMR and MD approaches revealed that the oligomers adopt an elongated, almost straight, structure, stabilized by inter-residue H-bonds, one of which is a non-conventional C-H...O hydrogen bond between H5 of the residue (i+1) and O3 of the residue (i). The structures position the C-2 substituents almost perpendicular to the oligosaccharide main chain axis, pointing to the bulk solvent and available for interactions with antibodies or other binding partners.