High-Affinity Copolymers Inhibit Digestive Enzymes by Surface Recognition

Patrick Gilles, Kirstin Wenck, Inga Stratmann, Michael Kirsch, Daniel Smolin, Torsten Schaller, Herbert de Groot, Arno Manfred Kraft, Thomas Schrader

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)
275 Downloads (Pure)


This account presents a general method for the construction of polymeric surface binders for digestion enzymes. Two prominent parts, namely the modification of the copolymer composition and the screening assay for the most powerful inhibitors are both amenable to parallelization. The concept hinges on the appropriate selection of amino-acid-selective comonomers, their free radical copolymerization, and subsequent screening of the resulting copolymer library for efficient enzyme inhibition. A microscale synthetic procedure for the copolymerization process was developed, which produces water-soluble affinity polymers that can be stored for years at room temperature. Initial parallel screening was conducted in standard enzyme assays to identify polymeric inhibitors, which were subsequently subjected to determination of IC50 values for their target enzyme. For all digestion enzymes except elastase a number of polymer inhibitors were found, some of which were selective towards one or two protein targets. Since the key monomers of the best inhibitors bind to amino acid residues in the direct vicinity of the active site, we conclude that efficient coverage of the immediate environment by the copolymers is critical. Strong interference with enzymatic activity is brought about by blocking the substrate access and product exit to and from the active site.
Original languageEnglish
Pages (from-to)1772–1784
Number of pages13
Issue number6
Early online date18 Apr 2017
Publication statusPublished - 12 Jun 2017


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