Synthesis and Structural Analysis of Aspergillus fumigatus Galactosaminogalactans Featuring α‐Galactose, α‐Galactosamine and α‐N‐Acetyl Galactosamine Linkages. (20th May 2020)

• Record Type: Journal Article
• Authors: Zhang, Yongzhen; Gómez‐Redondo, Marcos; Jiménez‐Osés, Gonzalo; Arda, Ana; Overkleeft, Herman S.; van der Marel, Gijsbert A.; Jiménez‐Barbero, Jesús; Codée, Jeroen D. C.
• Is Part Of: Angewandte Chemie. Volume 132:Number 31(2020)
• Page Start: 12846
• Page End: 12850
• Publication Date: 2020-05-20
• Subjects: conformational analysis -- glycosylation -- non-conventional hydrogen bond -- oligosaccharides -- stereoselectivity; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202003951
• Languages: English
• ISSNs: 0044-8249

Abstract

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. Abstract : The completely stereoselective assembly of fungal Aspergillus fumigatus galactosaminogalactans, incorporating α‐Gal, α‐GalN and α‐GalNac residues up to dodecasaccharides, is reported. Structural studies reveal a non‐canonical C−H⋅⋅⋅O hydrogen bond to stabilize the elongated, linear structure that displays the Gal‐functional groups to the outside of the polymer, available for interactions with binding partners.