Chemical and Chemo-Enzymatic Syntheses of Glycans Containing Ribitol Phosphate Scaffolding of Matriglycan
Chemical and Chemo-Enzymatic Syntheses of Glycans Containing Ribitol Phosphate Scaffolding of Matriglycan
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含有磷酸核糖醇基质聚糖支架的聚糖的化学和化学酶合成
DOI：
10.1021/acschembio.2c00181
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发表时间：
2022
影响因子：
4
通讯作者：
Endo Tamao
中科院分区：
文献类型：
--
作者：
Tamura Jun-ichi;Tamura Takahiro;Hoshino Shunsuke;Imae Rieko;Kato Ryuichi;Yokono Mizuki;Nagase Mao;Ohno Shiho;Manabe Noriyoshi;Yamaguchi Yoshiki;Manya Hiroshi;Endo Tamao
对核心M3 O-甘露糖基聚糖的核糖醇磷酸修饰对于α-肌营养不良聚糖的功能成熟很重要。区域和立体选择性地合成了包括串联核糖醇磷酸的核心M3 O-甘露糖聚糖的三种顺序延伸的部分结构：Rbo 5 P-3GalNAcβ、Rbo 5 P-1 Rbo 5 P-3GalNAcβ和Xylβ1- 4 Rbo 5 P-1 Rbo 5 P-3GalNAcβ（Rbo 5 P，d-核糖醇-5-磷酸; GalNAc，N-乙酰基-d-半乳糖胺; Xyl，d-木糖）。Rbo 5 P-3GalNAcβ的糖苷配基部分为对硝基苯基，可作为核糖醇磷酸转移酶（FKRP，fukutin-related protein）的底物，其产物在核糖醇木糖基转移酶1（RXYLT 1）、β 1，4-葡萄糖醛酸基转移酶1（B4 GAT 1）和类乙酰氨基葡萄糖基转移酶（LARGE）等一系列糖基转移酶的作用下被糖基化。配备有炔型糖苷配基的Rbo 5 P-3GalNAcβ对FKRP也有活性。在FKRP上获得的分子信息表明，Rbo 5 P-3GalNAcβ衍生物是Rbo 5 P转移的受体聚糖所需的最小单元，并可作为延长核心M3 O-甘露糖基聚糖的前体。
Ribitol phosphate modifications to the core M3O-mannosyl glycan are important for the functional maturation of α-dystroglycan. Three sequentially extended partial structures of the core M3O-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 withp-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 M3O-mannosyl glycan.