title: Synthesis and evaluation of di- and trimeric hydroxylamine-based β-(1→3)-glucan mimetics.
abstract: Di- and trimeric hydroxylamine-based mimetics of β-(1→3)-glucans have been accessed by an asymmetric synthesis route featuring an iterative double ring-closing reductive amination reaction. These oligomeric hydroxylamines are demonstrated to inhibit the staining of human neutrophils and of mouse macrophages by fluorescent anti-CR3 and anti-dectin-1 antibodies, respectively, and to stimulate phagocytosis, all in a linkage-dependent manner suggestive of binding to the lectin domains of complement receptor 3 (CR3) and dectin-1. The ability of these relatively short mimetics to bind to CR3 and dectin-1, as compared to the greater degree of polymerization required in β-(1→3)-glucans, is discussed in terms of the increased hydrophobicity of the α-face on replacement of the glycosidic bond by the hydroxylamine linkage.
authors.affiliation: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS , Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
authors.forename: Angélique
authors.initials: A
authors.lastname: Ferry
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Malik
authors.forename: Xavier
authors.initials: X
authors.lastname: Guinchard
authors.forename: Václav
authors.initials: V
authors.lastname: Vĕtvička
authors.forename: David
authors.initials: D
authors.lastname: Crich
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D060326:Chemistry Techniques, Synthetic; D019281:Dimerization; D006801:Humans; D019811:Hydroxylamine / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D037181:Lectins, C-Type / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D051379:Mice; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D047071:beta-Glucans / Q000737:chemistry*; D000099181:Dectin-1
chemical_list: D019811:Hydroxylamine; D037181:Lectins, C-Type; D016177:Macrophage-1 Antigen; D047071:beta-Glucans; D000099181:Dectin-1; C033363:beta-1,3-glucan