Development and use of a polymer-based antibody mimetic for specific targeting of fibroblast activation protein

Fibroblast activation protein (FAP) is a serine protease which is associated with cancer and recently also with other diseases such as rheumatoid arthritis or liver cirrhosis. Increased expression of FAP was observed in more than 90 % of epithelial cancers in contrast to its minimal expression levels in healthy tissues. FAP therefore represents a potential target for anti-cancer treatment as well as a diagnostic marker for various other diseases. In order to accomplish inhibition of FAP, a series of inhibitors was developed. The essential property of the inhibitors is their selectivity against dipeptidyl peptidase IV (DPP-IV), a homologue of FAP, which is expressed in majority of healthy tissues. This diploma thesis describes a novel research tool for characterization of FAP - a polymer conjugate containing FAP inhibitor as a targeting ligand, fluorophore for the visualization of the conjugate and biotin for its immobilization. The polymer conjugate functions as an antibody mimetic, which can be used in a variety of biochemical methods for detection, visualization and specific targeting of FAP. This study shows that the polymer conjugate selectively and effectively inhibits FAP with more than three orders of magnitude difference of the inhibition constant in comparison to DPP-IV. At the same time,..