Visualizing Trimming Dependence of Biodistribution and Kinetics with Homo- and Heterogeneous N-Glycoclusters on Fluorescent Albumin.
Visualizing Trimming Dependence of Biodistribution and Kinetics with Homo- and Heterogeneous N-Glycoclusters on Fluorescent Albumin.
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DOI：
10.1038/srep21797
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发表时间：
2016-02-23
影响因子：
4.6
通讯作者：
Tanaka K
中科院分区：
文献类型：
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作者：
Ogura A;Tahara T;Nozaki S;Morimoto K;Kizuka Y;Kitazume S;Hara M;Kojima S;Onoe H;Kurbangalieva A;Taniguchi N;Watanabe Y;Tanaka K
一系列的N-聚糖，每一个顺序修剪从双触角唾液酸聚糖，同源或异源有效地聚集在荧光白蛋白使用的方法相结合的应变促进的炔叠氮环化和6π-氮杂电环化。非侵入性体内动力学和解剖分析显示，第一次，聚糖依赖性的转变，从尿液到胆囊排泄介导的顺序修剪的非还原性末端唾液酸。进一步修剪的N-糖蛋白，特别是GlcNAc-和杂合双触角终止的同源物，被肝中的窦状内皮细胞和星状细胞选择性摄取，这对于肝纤维化的诊断和治疗至关重要。我们的糖簇策略不仅可以揭示以前未开发的N-聚糖修剪的细胞外功能，但将被归类为新出现的糖探针的诊断和治疗应用。
A series of N-glycans, each sequentially trimmed from biantennary sialoglycans, were homo- or heterogeneously clustered efficiently on fluorescent albumin using a method that combined strain-promoted alkyne-azide cyclization and 6π-azaelectrocyclization. Noninvasive in vivo kinetics and dissection analysis revealed, for the first time, a glycan-dependent shift from urinary to gall bladder excretion mediated by sequential trimming of non-reducing end sialic acids. N-glycoalbumins that were trimmed further, in particular, GlcNAc- and hybrid biantennary-terminated congeners, were selectively taken up by sinusoidal endothelial and stellate cells in the liver, which are critical for diagnosis and treatment of liver fibrillation. Our glycocluster strategy can not only reveal the previously unexplored extracellular functions of N-glycan trimming, but will be classified as the newly emerging glycoprobes for diagnostic and therapeutic applications.