Glycopeptides as Targets for Dendritic Cells: Exploring MUC1 Glycopeptides Binding Profile toward Macrophage Galactose-Type Lectin (MGL) Orthologs

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 muci...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2017-11, Vol.60 (21), p.9012-9021
Main Authors: Artigas, Gerard, Monteiro, João T, Hinou, Hiroshi, Nishimura, Shin-Ichiro, Lepenies, Bernd, Garcia-Martin, Fayna
Format: Article
Language:English
Subjects:
Animals
Dendritic Cells - immunology
Glycopeptides - immunology
Glycosylation
Humans
Lectins, C-Type - chemistry
Lectins, C-Type - metabolism
Mice
Mucin-1 - metabolism
Protein Binding
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Summary: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 (mMGL1). 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.
ISSN:0022-2623
1520-4804
DOI:10.1021/acs.jmedchem.7b01242