title: Chemoenzymatic Synthesis of Nonasulfated Tetrahyaluronan with a Paramagnetic Tag for Studying Its Complex with Interleukin-10.
abstract: Implants and artificial biomaterials containing sulfated hyaluronans have been shown to improve the healing of injured skin and bones. It is hypothesized that these effects are mediated by the binding of sulfated glycosaminoglycans (GAGs) to growth factors and cytokines, resulting in the sequestering of proteins to the wound healing site and in modulated protein activity. Given that no direct synthetic access to sulfated oligohyaluronans has been available, little is known about their protein binding and the structure of the resulting protein complexes. Here, the chemoenzymatic preparation of oligohyaluronans on the gram scale is described. Oligohyaluronans are converted into anomeric azides at the reducing end, enabling the attachment of analytical labels through an anomeric ligation reaction. A nonasulfated tetrahyaluronan-ethylenediaminetetraacetic acid derivative has been produced and used as a paramagnetic tag for the elucidation of the complex of this ligand with interleukin-10 using paramagnetic relaxation enhancement NMR analysis. The metal ion position is resolved with 1.0 Å, enabling a refined structural model of the complex.
authors.affiliation: Institute of Pharmacy-Medicinal Chemistry, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195, Berlin, Germany.|Institute of Medical Physics and Biophysics, Universität Leipzig, Härtelstr. 16/18, 04107, Leipzig, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Köhling
authors.affiliation: Institute of Medical Physics and Biophysics, Universität Leipzig, Härtelstr. 16/18, 04107, Leipzig, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Künze
authors.affiliation: Institute of Medical Physics and Biophysics, Universität Leipzig, Härtelstr. 16/18, 04107, Leipzig, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Lemmnitzer
authors.affiliation: Institute of Pharmacy-Medicinal Chemistry, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195, Berlin, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Bermudez
authors.affiliation: Institute of Pharmacy-Medicinal Chemistry, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195, Berlin, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wolber
authors.affiliation: Institute of Medical Physics and Biophysics, Universität Leipzig, Härtelstr. 16/18, 04107, Leipzig, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schiller
authors.affiliation: Institute of Medical Physics and Biophysics, Universität Leipzig, Härtelstr. 16/18, 04107, Leipzig, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Huster
authors.affiliation: Institute of Pharmacy-Medicinal Chemistry, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195, Berlin, Germany. joerg.rademann@fu-berlin.de.|Institute of Medical Physics and Biophysics, Universität Leipzig, Härtelstr. 16/18, 04107, Leipzig, Germany. joerg.rademann@fu-berlin.de.
authors.forename: Jörg
authors.identifier: http://orcid.org/0000-0001-6678-3165
authors.initials: J
authors.lastname: Rademann
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry*; D006025:Glycosaminoglycans / Q000737:chemistry* / Q000378:metabolism; D006820:Hyaluronic Acid / Q000138:chemical synthesis* / Q000737:chemistry*; D016753:Interleukin-10 / Q000737:chemistry*; D008024:Ligands; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D011485:Protein Binding
chemical_list: D001672:Biocompatible Materials; D006025:Glycosaminoglycans; D008024:Ligands; D016753:Interleukin-10; D006820:Hyaluronic Acid
keywords: carbohydrates; cytokines; growth factors; host-guest systems; protein structures