6533b826fe1ef96bd1285164

RESEARCH PRODUCT

Polymeric Selectin Ligands Mimicking Complex Carbohydrates: From Selectin Binders to Modifiers of Macrophage Migration

Figen Beceren-braunFrank TackeJens DerneddeMatthias BarzRudolf ZentelMatthias BartneckTwan LammersKai E. MoogElisa A. LiehnZhuojun WuLydia BraunHorst KunzNicole Mohr

subject

OligosaccharidesTyramine02 engineering and technologyLigands010402 general chemistry01 natural sciencesCatalysisFucoseInhibitory Concentration 50chemistry.chemical_compoundPolymethacrylic AcidsCell MovementHuman Umbilical Vein Endothelial CellsSide chainHumansTetrasaccharideMethacrylamideSialyl Lewis X AntigenCell adhesionCells CulturedMacrophagesGeneral ChemistrySurface Plasmon ResonanceFlow Cytometry021001 nanoscience & nanotechnologyIn vitro0104 chemical sciencesSialic acidMicroscopy Fluorescence MultiphotonNanomedicinechemistryBiochemistrySelectins0210 nano-technologySelectin

description

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 SLeX is 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.

yearjournalcountryeditionlanguage
2016-12-22Angewandte Chemie International Edition
https://doi.org/10.1002/anie.201610395