The FOLDAPPI (Foldamers against protein-protein interactions) project focused on interactions between interleukin 4 (IL-4) and its receptor. IL-4 is a key regulator of the immune system. Its significance to the FOLDAPPI project is its involvement in misguided immune reactions such as allergy and asthma. Despite its importance in autoimmune disease and being an obvious drug target, no small molecule inhibitor of IL-4 and its receptor has been reported so far. The project team developed aromatic amide foldamers derived from quinoline-carboxamide oligomers to potentially block the IL-4-receptor reaction. FOLDAPPI researchers developed a protocol to model the action of the foldamers developed by the project. They used a synthetic method to prepare specific libraries of quinoline-derived tetramers. The team also validated the chemistry behind the tethering of one of the foldamers on IL-4. To complete the procedures, an assay to test the foldamer-IL-4 interactions was formulated. Another physiologically important molecule came under FOLDAPPI scrutiny. The researchers screened for foldamer interaction with human carbonic anhydrase II. They also determined the crystal structure of this protein complexed with a foldamer. The work uncovered some unexpected protein-foldamer interactions. The theme of foldamer chemistry has been aired annually at conferences throughout Europe bringing together a diverse scientific community interested in these physiologically important molecules. FOLDAPPI research results have assembled a comprehensive knowledge platform that could lead to the development of new therapies for autoimmune disorders.
Foldamer, folding, interleukin-4, allergy, human carbonic anhydrase II