Glycopeptides as Targets for Dendritic Cells: Exploring MUC1 Glycopeptides Binding Profile toward Macrophage Galactose-Type Lectin (MGL) Orthologs
Glycopeptides as Targets for Dendritic Cells: Exploring MUC1 Glycopeptides Binding Profile toward Macrophage Galactose-Type Lectin (MGL) Orthologs
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DOI：
10.1021/acs.jmedchem.7b01242
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发表时间：
2017-11-09
影响因子：
7.3
通讯作者：
Garcia-Martin, Fayna
中科院分区：
文献类型：
--
作者：
Artigas, Gerard;Monteiro, Joao T.;Garcia-Martin, Fayna
巨噬细胞半乳糖型凝集素(MGL)识别病原体暴露的糖链。和恶性细胞。特别是，粘蛋白-1(MUC1)糖蛋白在几种癌症中呈现糖基化改变。为了评估不同的MGL同源基因识别粘蛋白中异常糖链核心的能力，我们将逝去场检测应用于一个多功能的MUC1样糖肽微阵列平台。在这里，由于结合是序列依赖的，我们证明了不仅糖而且多肽区域影响小鼠MGL1(RaMGL1)的识别。此外，我们观察到，对于所有三个MGL同源物，二价多糖的存在增加了结合。为了评估MGL同源糖肽结合物对MGL靶向的效用，我们使用小鼠树突状细胞进行了荧光素-MUC1摄取试验。二糖基化的MUC1多肽优先内化成依赖于MGL的方式，从而显示了二价MGL靶向的效用。这些发现可能与通过MGL靶向树突状细胞的抗肿瘤疫苗的合理设计有关。
The macrophage galactose-type lectin (MGL) recognizes glycan moieties exposed by pathogens. and malignant cells. Particularly, mucin-1 (MUC1) glycoprotein presents an altered glycosylation in several cancers. To estimate the ability of distinct MGL orthologs to recognize aberrant glycan cores in mucins, we applied evanescent-field detection to a versatile MUC1-like glycopeptide microarray platform. Here, as binding was sequence-dependent, we demonstrated that not only sugars but also peptide region impact the recognition of murine MGL1 (raMGL1). In addition, we observed for all three MGL orthologs that divalent glycan presentation increased the binding. To assess the utility of the glycopeptide binders of the MGL orthologs for MGL targeting, we performed uptake assays with fluorescein-MUC1 using murine dendritic cells. A diglycosylated MUC1 peptide was preferentially internalized in an MGL-dependent fashion, thus showing the utility for divalent MGL targeting. These findings may be relevant to a rational design of antitumor vaccines targeting dendritic cells via MGL.