Chemical and Chemo-Enzymatic Syntheses of Glycans Containing Ribitol Phosphate Scaffolding of Matriglycan.

Jun-Ichi Tamura, Takahiro Tamura, Shunsuke Hoshino, Rieko Imae, Ryuichi Kato, Mizuki Yokono, Mao Nagase, Shiho Ohno, Noriyoshi Manabe, Yoshiki Yamaguchi, Hiroshi Manya, Tamao Endo

ACS chemical biology 2022 Jun 17

filter terms:

Ribitol phosphate modifications to the core M3 O-mannosyl glycan are important for the functional maturation of α-dystroglycan. Three sequentially extended partial structures of the core M3 O-mannosyl glycan including a tandem ribitol phosphate were regio- and stereo-selectively synthesized: Rbo5P-3GalNAcβ, Rbo5P-1Rbo5P-3GalNAcβ, and Xylβ1-4Rbo5P-1Rbo5P-3GalNAcβ (Rbo5P, d-ribitol-5-phosphate; GalNAc, N-acetyl-d-galactosamine; Xyl, d-xylose). Rbo5P-3GalNAcβ with p-nitrophenyl at the aglycon part served as a substrate for ribitol phosphate transferase (FKRP, fukutin-related protein), and its product was glycosylated by the actions of a series of glycosyltransferases, namely, ribitol xylosyltransferase 1 (RXYLT1), β1,4-glucuronyltransferase 1 (B4GAT1), and like-acetyl-glucosaminyltransferase (LARGE). Rbo5P-3GalNAcβ equipped with an alkyne-type aglycon was also active for FKRP. The molecular information obtained on FKRP suggests that Rbo5P-3GalNAcβ derivatives are the minimal units required as the acceptor glycan for Rbo5P transfer and may serve as a precursor for the elongation of the core M3 O-mannosyl glycan.

Citation

Jun-Ichi Tamura, Takahiro Tamura, Shunsuke Hoshino, Rieko Imae, Ryuichi Kato, Mizuki Yokono, Mao Nagase, Shiho Ohno, Noriyoshi Manabe, Yoshiki Yamaguchi, Hiroshi Manya, Tamao Endo. Chemical and Chemo-Enzymatic Syntheses of Glycans Containing Ribitol Phosphate Scaffolding of Matriglycan. ACS chemical biology. 2022 Jun 17;17(6):1513-1523