Modular Design of Small Enzymatic Reaction Networks Based on Reversible and Cleavable Inhibitors.

Angew Chem Int Ed Engl

Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, Nijmegen, 6525, AJ, The Netherlands.

Published: October 2019

AI Article Synopsis

  • Systems chemistry focuses on recreating the complex functions of living systems through chemical reaction networks with specific dynamic behaviors.
  • The study introduces reversible, cleavable peptide inhibitors to connect proteolytic enzymatic activity into basic network structures.
  • As a demonstration, various mechanisms were explored, including auto-activation leading to sigmoidal enzymatic responses and designing cascades with innovative phosphorylated peptides that can be activated by phosphatases.

Article Abstract

Systems chemistry aims to mimic the functional behavior of living systems by constructing chemical reaction networks with well-defined dynamic properties. Enzymes can play a key role in such networks, but there is currently no general and scalable route to the design and construction of enzymatic reaction networks. Here, we introduce reversible, cleavable peptide inhibitors that can link proteolytic enzymatic activity into simple network motifs. As a proof-of-principle, we show auto-activation topologies producing sigmoidal responses in enzymatic activity, explore cross-talk in minimal systems, design a simple enzymatic cascade, and introduce non-inhibiting phosphorylated peptides that can be activated using a phosphatase.

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Source
http://dx.doi.org/10.1002/anie.201907995DOI Listing

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