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Hersel, Ulrich (2007)
Publisher: Technische Universität München
Languages: German
Types: Doctoral thesis
Subjects: Zelladhäsion;Biomaterial;RGD;Peptid;Integrin;Multimer;Tumor;Tumordiagnose;Radiomarkierung;Radioiod;Titan;Osteoblasten;Oberfläche;Calciumphosphat;Hydroxylapatit;PET, cell adhesion;biomaterial;RGD;peptide;integrin;multimer;tumor diagnostics;tumor targeting;imaging;radiolabel;radioiodine;titanium;osteoblasts;surface;calcium phosphate;hydroxyapatite;PET, Chemie
ddc: ddc:540
Durch RGD-Peptide mit oberflächenadhäsiven Ankergruppen lassen sich Biomaterialoberflächen für die integrinvermittelte Zelladhäsion erzeugen. Eine Vielzahl von monomeren und multimeren cyclo-RGD-Peptiden mit verschiedenen Ankergruppen, u. a. für Titan und Calciumphosphat, wurden nach den Methoden der Peptidfestphasensynthese synthetisiert. Mit verzweigten, multimeren RGD-Peptiden und verbesserten Ankergruppen konnte die Adhäsion von Osteoblasten bzw. Chondrocyten auf Titan, Calciumphosphat (Hydroxylapatit), Gold und PMMA in vitro effektiv gesteigert werden. Für bildgebende Verfahren in der Tumordiagnostik wie z. B. PET wurden RGD-Peptide über chemoselektive Oximligation mit einer radiomarkierbaren Stannylkomponente verknüpft. Radioiodierte multimere RGD-Peptide zeigten gute Tumoranreicherung und Tumor/Organ-Verhältnisse in tumortragenden Mäusen in vivo. Integrin mediated cell adhesion on biomaterial surfaces can be greatly enhanced by cell adhesive RGD peptides. A variety of monomeric and multimeric cyclic RGD peptides was synthesized by means of solid phase peptide synthesis. Besides a cell adhesive RGD moiety an anchoring group for immobilization of the peptides e. g. on titanium or calcium phosphate surfaces was introduced. Branched multimeric RGD peptides as well as RGD peptides having improved anchoring groups significantly enhanced adhesion of osteoblasts and chondrocytes on titanium, calcium phosphate (hydroxyapatite), gold and PMMA in vitro. For tumor imaging, e.g. by PET, RGD peptides were linked to a stannyl compound by chemoselective oxime ligation. The stannyl compound is a precursor for radioiodination. Radioiodinated multimeric RGD peptides show enhanced accumulation in tumors and higher tumor/tissue ratios in tumor bearing mice in vivo.
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