Modular Design of Small Enzymatic Reaction Networks Based on Reversible and Cleavable Inhibitors
Autor: | Aleksandr A. Pogodaev, Wilhelm T. S. Huck, Miglė Jakštaitė, Marijn J. Hollander, Cristina Lía Fernández Regueiro |
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Rok vydání: | 2019 |
Předmět: |
chemistry.chemical_classification
010405 organic chemistry business.industry Phosphatase Peptide General Medicine General Chemistry Modular design 010402 general chemistry Network topology 01 natural sciences Combinatorial chemistry Catalysis Cell Physiological Phenomena Enzymes 0104 chemical sciences Living systems Enzyme chemistry Biomimetics Biocatalysis business Metabolic Networks and Pathways Physical Organic Chemistry |
Zdroj: | Angewandte Chemie. International Edition, 58, 41, pp. 14539-14543 Angewandte Chemie. International Edition, 58, 14539-14543 |
ISSN: | 1521-3773 1433-7851 |
DOI: | 10.1002/anie.201907995 |
Popis: | 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. |
Databáze: | OpenAIRE |
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