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Issue 5, 2015
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Molecular glues for manipulating enzymes: trypsin inhibition by benzamidine-conjugated molecular glues

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Abstract

Water-soluble bioadhesive polymers bearing multiple guanidinium ion (Gu+) pendants at their side-chain termini (Gluen–BA, n = 10 and 29) that were conjugated with benzamidine (BA) as a trypsin inhibitor were developed. The Gluen–BA molecules are supposed to adhere to oxyanionic regions of the trypsin surface, even in buffer, via a multivalent Gu+/oxyanion salt-bridge interaction, such that their BA group properly blocks the substrate-binding site. In fact, Glue10–BA and Glue29–BA exhibited 35- and 200-fold higher affinities for trypsin, respectively, than a BA derivative without the glue moiety (TEG–BA). Most importantly, Glue10–BA inhibited the protease activity of trypsin 13-fold more than TEG–BA. In sharp contrast, mGlue27–BA, which bears 27 Gu+ units along the main chain and has a 5-fold higher affinity than TEG–BA for trypsin, was inferior even to TEG–BA for trypsin inhibition.

Graphical abstract: Molecular glues for manipulating enzymes: trypsin inhibition by benzamidine-conjugated molecular glues

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Publication details

The article was received on 10 Feb 2015, accepted on 16 Mar 2015 and first published on 18 Mar 2015


Article type: Edge Article
DOI: 10.1039/C5SC00524H
Citation: Chem. Sci., 2015,6, 2802-2805
  • Open access: Creative Commons BY license
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    Molecular glues for manipulating enzymes: trypsin inhibition by benzamidine-conjugated molecular glues

    R. Mogaki, K. Okuro and T. Aida, Chem. Sci., 2015, 6, 2802
    DOI: 10.1039/C5SC00524H

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