Artificial Zymogen Based on Protein-Polymer Hybrids
Murata H. Kapil K. Kaupbayeva B. Russell A.J. Dordick J.S. Matyjaszewski K.
11 November 2024American Chemical Society
Biomacromolecules
2024#25Issue 117433 - 7445 pp.
This study explores the synthesis and application of artificial zymogens using protein-polymer hybrids to mimic the controlled enzyme activation observed in natural zymogens. Pro-trypsin (pro-TR) and pro-chymotrypsin (pro-CT) hybrids were engineered by modifying the surfaces of trypsin (TR) and chymotrypsin (CT) with cleavable peptide inhibitors utilizing surface-initiated atom transfer radical polymerization. These hybrids exhibited 70 and 90% reductions in catalytic efficiency for pro-TR and pro-CT, respectively, due to the inhibitory effect of the grafted peptide inhibitors. The activation of pro-TR by CT and pro-CT by TR resulted in 1.5- and 2.5-fold increases in enzymatic activity, respectively. Furthermore, the activated hybrids triggered an enzyme activation cascade, enabling amplification of activity through a dual pro-protease hybrid system. This study highlights the potential of artificial zymogens for therapeutic interventions and biodetection platforms by harnessing enzyme activation cascades for precise control of catalytic activity.
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Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, 15213, PA, United States
National Laboratory Astana, Nazarbayev University, Astana, 010000, Kazakhstan
Amgen Research, 1 Amgen Center Drive, Thousand Oaks, 91320, CA, United States
Department of Chemical and Biological Engineering, Center for Biotechnology & Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, 12180, NY, United States
Department of Chemistry
National Laboratory Astana
Amgen Research
Department of Chemical and Biological Engineering
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