Julia Liebscher, Joerg Karl Teßmar, Jürgen Groll

• The physical and chemical stability of peptides for biomedical applications can be greatly enhanced through the conjugation of polymers. A well‐known but rather underemployed selective coupling functionality is the azlactone group, which readily reacts with a number of different nucleophiles without the need for activation and the formation of any by‐products. For example, azlactone functional polymers are used to react with peptides and proteins, rich in amino and thiol groups, to form polymeric beads for affinity‐based column chromatography.The physical and chemical stability of peptides for biomedical applications can be greatly enhanced through the conjugation of polymers. A well‐known but rather underemployed selective coupling functionality is the azlactone group, which readily reacts with a number of different nucleophiles without the need for activation and the formation of any by‐products. For example, azlactone functional polymers are used to react with peptides and proteins, rich in amino and thiol groups, to form polymeric beads for affinity‐based column chromatography. So far, side chain functional azlactone polymers have been mainly synthesized by radical polymerization using 2‐vinyl‐4,4‐dimethyl azlactone together with different acrylate monomers. Here, a new azlactone precursor equipped with a functional thiol is presented, which can be attached to any vinyl functional polymer by thiol–ene chemistry. Subsequently, the formation of the reactive azlactone ring can be performed in situ at high conversion rate without the need for illumination. This approach is tested on an azlactone side functional poly(2‐oxazoline) by coupling amine containing molecules including a model peptide and is proven via \(^1\)H NMR spectroscopy, IR spectroscopy, as well as HPLC measurements.…