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Chemische Modifizierung von Proteinen zur Charakterisierung von Matrix-Protein-Interaktionen

Prof. Dr. Annette Beck-Sickinger

Im geplanten Projekt sollen die biokompatiblen Eigenschaften von Implantaten verbessern werden. Hierfür werden zwei Ansätze gewählt:

Durch spezifische Immobilisierung von Proteinmediatoren soll das Einwachsen der Implantate in das Gewebe verbessert werden. Hierfür sollen Mediatoren z. B. mit ECM-Segmenten modifiziert und mit Hilfe von spezifisch-bindenden Peptiden an Implantate gekoppelt werden.

Um das entzündungsauslösende Potential eines beschichteten Implantates abzuschätzen, soll seine Interaktion mit und das Freisetzungspotential von Chemokinen aus Zellen untersucht werden. Die hierfür benötigten modifizierten und natürlichen Chemokine, z. B. Interleukin-8 werden hergestellt und die Interaktion mit neuartigen Materialien sowie ECM-Segmenten quantifiziert.

Abbildung: Struktur eines typischen Chemokins

 

Projektrelevante Publikationen

  1. Pagel M, Beck-Sickinger AG. Multifunctional biomaterial coatings: synthetic challenges and biological activity. Biol Chem. 2016;398:3-22.
  2. Gladytz A, John T, Gladytz T, Hassert R, Pagel M, Risselada HJ, Naumov S, Beck-Sickinger AG, Abel B. Peptides@mica: from affinity to adhesion mechanism. Phys Chem Chem Phys. 2016;18:23516-27.
  3. Panitz N, Theisgen S, Samsonov SA, Gehrcke JP, Baumann L, Bellmann-Sickert K, Köhling S, Pisabarro MT, Rademann J, Huster D, Beck-Sickinger AG. The structural investigation of gly-cosaminoglycan binding to CXCL12 displays distinct interaction sites. Glycobiology 2016; doi: 10.1016/j.actbio.2016.08.030 [Epub ahead of print].
  4. Pagel M, Meier R, Braun K, Wiessler M, Beck-Sickinger AG. On-resin Diels-Alder reaction with inverse electron demand: an efficient ligation method for complex peptides with a varying spac-er to optimize cell adhesion. Org Biomol Chem. 2016;14:4809-16.
  5. Pagel M, Hassert R, John T, Braun K, Wießler M, Abel B, Beck-Sickinger AG. Multifunctional coating improves cell adhesion on titanium by using cooperatively acting peptides. Angew Chem Int Ed Engl. 2016;55:4826-30.
  6. Ansorge M, Rastig N, Steinborn R, König T, Baumann L, Möller S, Schnabelrauch M, Cross M, Werner C, Beck-Sickinger AG, Pompe T. Short-range cytokine gradients to mimic paracrine cell interactions in vitro. J Control Release. 2016;224:59-68.
  7. Saalbach A, Tremel J, Herbert D, Schwede K, Wandel E, Schirmer C, Anderegg U, Beck-Sickinger AG, Heiker JT, Schultz S, Magin T, Simon JC. Anti-inflammatory action of keratino-cyte-derived vaspin: relevance for the pathogenesis of psoriasis. Am J Pathol. 2016;186:639-51.
  8. Steinhagen M, Hoffmeister PG, Nordsieck K, Hötzel R, Baumann L, Hacker MSchulz-Siegmund MBeck-Sickinger AG. Matrix metalloproteinase 9 (MMP-9) mediated release of MMP-9 resistant stromal cell-derived factor 1? (SDF-1?) from surface modified polymer films. ACS Appl Mater Interfaces. 2014; 6, 5891-99
  9. Beck-Sickinger AG; Panitz N. Semi synthesis of chemokines.Curr Opin Chem Biol. 2014; 22C, 100-107
  10. Mattern A, Zellmann T, Beck-Sickinger AG. Processing, Signaling, and Physiological Function of Chemerin. IUBMB Life. 2014; 66, 19-26
  11. Steinhagen M, Hoffmeister PG, Nordsieck K, Hötzel R, Baumann L, Hacker MC, Schulz-Siegmund M, Beck-Sickinger AG. Matrix metalloproteinase 9 (MMP-9) mediated release of MMP-9 resistant stromal cell-derived factor 1alpha(SDF-1alpha) from surface modified polymer films. ACS Appl Mater Interfaces. 2014; 6(8):5891-9.
  12. Baer A, de Sena Oliveira I, Steinhagen M, Beck-Sickinger AG, Mayer G. Slime protein profiling: a non-invasive tool for species identification in Onychophora (velvet worms). J Zoolog Syst Evol Res. 2014;52(4), 265-272.
  13. Baumann L, Beck-Sickinger AG. Photoactivatable chemokines--controlling protein activity by light. Angew Chem Int Ed Engl. 2013;52:9550-3.
  14. Hassert R, Pagel M, Ming Z, Häupl T, Abel B, Braun K, Wiessler M, Beck-Sickinger AG. Biocompatible silicon surfaces through orthogonal click chemistries and a high affinity silicon oxide binding peptide. Bioconj Chem. 2012;23:2129-37.
  15. Hassert R, Hoffmeister PG, Pagel M, Hacker M, Schulz-Siegmund M, Beck-Sickinger AG. On-resin synthesis of an acylated and fluorescence-labeled cyclic integrin ligand for modification of poly-(lactid-coglycolic-acid). Chem Biodivers. 2012;9:2648-58.
  16. Nordsieck K, Pichert A, Samsonov SA, Thomas L, Berger C, Pisabarro MT, Huster D, Beck-Sickinger AG. Residue 75 of Interleukin-8 is Curicial for the Interaction with Glycosaminoglycans.ChemBioChem. 2012; 13:2558-66.
  17. Baumann L, Prokoph S, Gabriel C, Freudenberg U, Werner C, Beck-Sickinger AG. A novel, biased-like SDF-1 derivative acts synergistically with starPEG-based heparin hydrogels and improves eEPC migration in vitro. J Control Release. 2012;162:68-75.
  18. Pichert A, Samsonov SA, Theisgen S, Thomas L, Baumann L, Schiller J, Beck-Sickinger AG, Huster D, Pisabarro MT. Characterization of the interaction of the interaction of Interleukin-8 with hyaluronan, chondroitin sulfate, dermatan sulfate, and their sulfated derivatives by spectroscopy and molecular modelling. Glycobiology. 2012;22:134-45.
  19. Steinhagen M, Holland-Nell K, Meldal M, Beck-Sickinger AG. Simultaneous "one pot" expressed protein ligation and CuI-catalyzed azide/alkyne cycloaddition for protein immobilization. ChemBioChem. 2011;12:2426-30.
  20. Bellmann-Sickert K, Beck-Sickinger AG. Palmitoylated SDF1alpha shows increased resistance against proteolytic degradation in liver homogenates. ChemMedChem. 2011;6:193-200.
  21. Bellmann-Sickert K, Baumann L, Beck-Sickinger AG. Selective Labelling of Stromal Cell-Derived Factors 1 a with Carboxyfluorescencein to Study Receptor Internalisation. J Pept Sci. 2010;16:568-74.
  22. Bellmann-Sickert K, Beck-Sickinger AG. Peptide drugs to target G protein-coupled receptors. Trends Pharmacol Sci. 2010;31:434-41.
  23. Baumann L, Beck-Sickinger AG. Identification of a potential modification site of stromal-derived factor 1. Biopolymers. 2010;94:771-8.
  24. Bachmann M, Goede K, Beck-Sickinger AG, Grundmann M, Irbäck A, Janke W. Microscopic mechanism of specific peptide adhesion to semiconductor substrates. Angew Chem Int Ed Engl. 2010;49:9530-33.
  25. David R, Günther R, Baumann L, Lühmann T, Hofmann H-J, Seebach D, Beck-Sickinger AG. Artificial Chemokines – Combining Chemistry and Molecular Biology for the Elucidation of Interleukin-8 Functionality, J Am Chem Soc. 2008;130:15311-7.
  26. Frommhold D, Ludwig A, Bixel MG, Zarbock A, Babushkina I, Weissinger M, Cauwenberghs S, Lange-Sperandio B, Ellies LG, Marth JD, Beck-Sickinger AG, Zernecke A, Weber C, Vestweber D, Ley K, Sperandio M. Sialyltransferase ST3Gal-IV controls CXCR2-mediated firm leukocyte arrest during inflammation. J Exp Med. 2008;205:1435-46.
  27. Ralf David and Annette G. Beck-Sickinger (2007) Identification of the dimerisation interface of human interleukin-8 by IL-8-variants containing the photoactivatable amino acid benzoyl-phenylalanine, Eur. Biophys. J. 36, 385-391.
  28. Rosenkilde MM, David R, Oerlecke I, Geumann U, Beck-Sickinger AG, Schwartz TW. Conformational constraining of inactive and active states of a 7TM receptor by metal-ion site engineering in the top of TM . Mol Pharmacol. 2006;70:1892-1901.
  29. David R, Richter MPO, Beck-Sickinger AG. Expressed protein ligation: methods and application. Eur J Biochem. 2004;271:663-77.
  30. Machova Z, von Eggelkraut-Gottanka R, Wehofsky N, Bordusa F, Beck-Sickinger AG. (2003) Expressed enzymatic ligation: a new approach for the synthesis of chemically modified proteins, Angew Chem Int Ed. 2003;42:4916-4918 (VIP-paper).
  31. David R, Machova Z, Beck-Sickinger AG. Semisynthesis and application of carboxyfluorescein-labeled biologically active human interleukin-8. Biol Chem. 2003;384:1619-1630.