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

Kai E. Moog, Matthias Barz, Matthias Bartneck, Figen Beceren-Braun, Nicole Mohr, Zhuojun Wu, Lydia Braun, Jens Dernedde, Elisa A. Liehn, Frank Tacke, Twan Lammers, Horst Kunz, Rudolf Zentel

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

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.

Original languageEnglish
Pages (from-to)1416-1421
Number of pages6
JournalAngewandte Chemie - International Edition
Volume56
Issue number5
DOIs
StatePublished - 24 Jan 2017
Externally publishedYes

Keywords

  • PHPMA
  • glycopolymers
  • nanomedicine
  • polymer–carbohydrate conjugates
  • sialyl-Lewismimetics

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