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Synthesis and Structural Analysis of Aspergillus fumigatus Galactosaminogalactans Featuring α‐Galactose, α‐Galactosamine and α‐ N ‐Acetyl Galactosamine Linkages
Author(s) -
Zhang Yongzhen,
GómezRedondo Marcos,
JiménezOsés Gonzalo,
Arda Ana,
Overkleeft Herman S.,
Marel Gijsbert A.,
JiménezBarbero Jesús,
Codée Jeroen D. C.
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202003951
Subject(s) - galactosamine , chemistry , residue (chemistry) , aspergillus fumigatus , oligosaccharide , galactose , stereochemistry , hydrogen bond , biochemistry , molecule , organic chemistry , microbiology and biotechnology , biology
Abstract Galactosaminogalactan (GAG) is a prominent cell wall component of the opportunistic fungal pathogen Aspergillus fumigatus . GAG is a heteropolysaccharide composed of α‐1,4‐linked galactose, galactosamine and N ‐acetylgalactosamine residues. To enable biochemical studies, a library of GAG‐fragments was constructed featuring specimens containing α‐galactose‐, α‐galactosamine and α‐ N ‐acetyl galactosamine linkages. Key features of the synthetic strategy include the use of di‐ tert ‐butylsilylidene directed α‐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.