title: Polymeric Selectin Ligands Mimicking Complex Carbohydrates: From Selectin Binders to Modifiers of Macrophage Migration.
abstract: Novel polymeric cell adhesion inhibitors were developed in which the selectin tetrasaccharide sialyl-LewisX(SLeX) is multivalently presented on a biocompatible poly(2-hydroxypropyl)methacrylamide (PHPMA) backbone either alone (P1) or in combination with O-sulfated tyramine side chains (P2). For comparison, corresponding polymeric glycomimetics were prepared in which the crucial "single carbohydrate" substructures fucose, galactose, and sialic acid side chains were randomly linked to the PHPMA backbone (P3 or P4 (O-sulfated tyramine)). All polymers have an identical degree of polymerization, as they are derived from the same precursor polymer. Binding assays to selectins, to activated endothelial cells, and to macrophages show that polyHPMA with SLeXis an excellent binder to E-, L-, and P-selectins. However, mimetic P4 can also achieve close to comparable binding affinities in in vitro measurements and surprisingly, it also significantly inhibits the migration of macrophages; this provides new perspectives for the therapy of severe inflammatory diseases.
authors.affiliation: Institut für Organische Chemie, Johannes Gutenberg-Universität Mainz, Duesbergweg 10-14, 55128, Mainz, Germany.
authors.forename: Kai E
authors.initials: KE
authors.lastname: Moog
authors.affiliation: Institut für Organische Chemie, Johannes Gutenberg-Universität Mainz, Duesbergweg 10-14, 55128, Mainz, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Barz
authors.affiliation: Medizinische Klinik III, Uniklinikum Aachen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Bartneck
authors.affiliation: Institut für Laboratoriumsmedizin, Klinische Chemie und Pathobiochemie, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Figen
authors.initials: F
authors.lastname: Beceren-Braun
authors.affiliation: Institut für Organische Chemie, Johannes Gutenberg-Universität Mainz, Duesbergweg 10-14, 55128, Mainz, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Mohr
authors.affiliation: Institut für Molekulare Herz-Kreislaufforschung (IMCAR), Uniklinikum Aachen, Germany.
authors.forename: Zhuojun
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Institut für Organische Chemie, Johannes Gutenberg-Universität Mainz, Duesbergweg 10-14, 55128, Mainz, Germany.
authors.forename: Lydia
authors.initials: L
authors.lastname: Braun
authors.affiliation: Institut für Laboratoriumsmedizin, Klinische Chemie und Pathobiochemie, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Dernedde
authors.affiliation: Institut für Molekulare Herz-Kreislaufforschung (IMCAR), Uniklinikum Aachen, Germany.
authors.forename: Elisa A
authors.initials: EA
authors.lastname: Liehn
authors.affiliation: Medizinische Klinik III, Uniklinikum Aachen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Tacke
authors.affiliation: Institut für Experimentelle Molekulare Bildgebung (ExMI), Uniklinikum Aachen, Germany.
authors.forename: Twan
authors.initials: T
authors.lastname: Lammers
authors.affiliation: Institut für Organische Chemie, Johannes Gutenberg-Universität Mainz, Duesbergweg 10-14, 55128, Mainz, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Kunz
authors.affiliation: Institut für Organische Chemie, Johannes Gutenberg-Universität Mainz, Duesbergweg 10-14, 55128, Mainz, Germany.
authors.forename: Rudolf
authors.identifier: 0000-0001-9206-6047
authors.initials: R
authors.lastname: Zentel
mesh_terms: D002465:Cell Movement; D002478:Cells, Cultured; D005434:Flow Cytometry; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D036641:Microscopy, Fluorescence, Multiphoton; D050997:Nanomedicine; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism*; D011109:Polymethacrylic Acids / Q000737:chemistry; D019087:Selectins / Q000737:chemistry / Q000378:metabolism*; D000080506:Sialyl Lewis X Antigen; D020349:Surface Plasmon Resonance; D014439:Tyramine / Q000737:chemistry
chemical_list: D008024:Ligands; D009844:Oligosaccharides; D011109:Polymethacrylic Acids; D019087:Selectins; D000080506:Sialyl Lewis X Antigen; C011533:Duxon; D014439:Tyramine
keywords: PHPMA; glycopolymers; nanomedicine; polymer-carbohydrate conjugates; sialyl-Lewisx mimetics