title: Glycodendrimers and Modified ELISAs: Tools to Elucidate Multivalent Interactions of Galectins 1 and 3.
abstract: Multivalent protein-carbohydrate interactions that are mediated by sugar-binding proteins, i.e., lectins, have been implicated in a myriad of intercellular recognition processes associated with tumor progression such as galectin-mediated cancer cellular migration/metastatic processes. Here, using a modified ELISA, we show that glycodendrimers bearing mixtures of galactosides, lactosides, and N-acetylgalactosaminosides, galectin-3 ligands, multivalently affect galectin-3 functions. We further demonstrate that lactose functionalized glycodendrimers multivalently bind a different member of the galectin family, i.e., galectin-1. In a modified ELISA, galectin-3 recruitment by glycodendrimers was shown to directly depend on the ratio of low to high affinity ligands on the dendrimers, with lactose-functionalized dendrimers having the highest activity and also binding well to galectin-1. The results depicted here indicate that synthetic multivalent systems and upfront assay formats will improve the understanding of the multivalent function of galectins during multivalent protein carbohydrate recognition/interaction.
authors.affiliation: Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT 59717, USA. mlwolfenden@gmail.com.
authors.forename: Mark
authors.initials: M
authors.lastname: Wolfenden
authors.affiliation: Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT 59717, USA. jon.cousin@chemistry.montana.edu.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cousin
authors.affiliation: The Departments of Oncology and Pathology, School of Medicine, Wayne State University, Detroit, MI 48201, USA. makkerp@karmanos.org.
authors.forename: Pratima
authors.initials: P
authors.lastname: Nangia-Makker
authors.affiliation: The Departments of Oncology and Pathology, School of Medicine, Wayne State University, Detroit, MI 48201, USA. raza@karmanos.org.
authors.forename: Avraham
authors.initials: A
authors.lastname: Raz
authors.affiliation: Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT 59717, USA. mcloninger@chemistry.montana.edu.
authors.forename: Mary
authors.initials: M
authors.lastname: Cloninger
mesh_terms: D001665:Binding Sites; D050091:Dendrimers / Q000737:chemistry / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D037483:Galectin 1 / Q000737:chemistry / Q000378:metabolism*; D037502:Galectin 3 / Q000737:chemistry / Q000378:metabolism*; D006027:Glycosides / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding
chemical_list: D050091:Dendrimers; D037483:Galectin 1; D037502:Galectin 3; D006027:Glycosides