Synthesis of a pentasaccharide and neoglycoconjugates related to fungal α-(1→3)-glucan and their use in the generation of antibodies to trace Aspergillus fumigatus cell wall.
3-Aminopropyl α-(1→3)-pentaglucoside, a fragment of α-(1→3)-glucan of the cell wall of Aspergillus fumigatus, has been synthesized in a blockwise approach. The application of mono- and disaccharide N-phenyltrifluoroacetimidates bearing a stereodirecting 6-O-benzoyl group was essential for stereoselective α-glucosylations. In the products, p-methoxyphenyl and levulinoyl groups served as orthogonal protecting groups for the anomeric position and 3-OH group, respectively. Their removal from shared blocks led to donors and acceptors that were used for the synthesis of pentasaccharides. Coupling of free α-(1→3)-pentaglucoside with biotin and bovine serum albumin (BSA) gave glycoconjugate tools for mycological studies. Immunization of mice with the BSA conjugate induced the generation of antibodies that recognize α-(1→3)-glucan on A. fumigatus cell wall and distinguish its morphotypes. This discovery represents a first step to the development of a diagnostic test system and a vaccine to detect and fight this life-threatening pathogen.
Laboratory of Glycoconjugate Chemistry, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, 119991 Moscow (Russia).
Bozhena S
BS
Komarova
Maria V
MV
Orekhova
Yury E
YE
Tsvetkov
Remi
R
Beau
Vishukumar
V
Aimanianda
Jean-Paul
JP
Latgé
Nikolay E
NE
Nifantiev
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001232:Aspergillus fumigatus / Q000378:metabolism*; D001710:Biotin / Q000737:chemistry / Q000276:immunology; D002417:Cattle; D002473:Cell Wall / Q000378:metabolism; D005260:Female; D005936:Glucans / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D006001:Glycoconjugates / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000276:immunology
D000906:Antibodies; D005936:Glucans; D006001:Glycoconjugates; D009844:Oligosaccharides; D012710:Serum Albumin, Bovine; D001710:Biotin
carbohydrates; glycoconjugates; glycosylation; imaging agents; protecting groups