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Polymeric Selectin Ligands Mimicking Complex Carbohydrates: From Selectin Binders to Modifiers of Macrophage Migration
Author(s) -
Moog Kai E.,
Barz Matthias,
Bartneck Matthias,
BecerenBraun Figen,
Mohr Nicole,
Wu Zhuojun,
Braun Lydia,
Dernedde Jens,
Liehn Elisa A.,
Tacke Frank,
Lammers Twan,
Kunz Horst,
Zentel Rudolf
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201610395
Subject(s) - tetrasaccharide , selectin , chemistry , methacrylamide , sulfation , glycan , biochemistry , in vitro , polymer , adhesion , copolymer , organic chemistry , polysaccharide , glycoprotein , acrylamide
Novel polymeric cell adhesion inhibitors were developed in which the selectin tetrasaccharide sialyl‐Lewis X (SLe X ) 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 SLe X 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.