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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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Article information


Submitted
10 Feb 2015
Accepted
16 Mar 2015
First published
18 Mar 2015

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2015,6, 2802-2805
Article type
Edge Article
Author version available

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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