Full Thermal Switching of Enzymes by Thermoresponsive Poly(2‐oxazoline)‐Based Enzyme Inhibitors

• Published in: Chemistry : a European journal Vol. 26; no. 59; pp. 13367 - 13371
• Main Authors: Hijazi, Montasser, Türkmen, Esra, Tiller, Joerg C.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 21-10-2020; John Wiley and Sons Inc
• Subjects: Biocatalysts; Biotechnology; Chemistry; Communication; Communications; Enzymatic activity; Enzyme activity; Enzyme inhibitors; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Enzymes; functional polymer end groups; Iminodiacetic acid; Laccase; lower critical solution temperature polymers; Oxazoles - chemistry; Peroxidase; poly(2-oxazoline); Polymers; Polyoxazolines; Switching; Temperature; thermoresponsive; poly(2-oxazoline); lower critical solution temperature polymers; thermoresponsive; functional polymer end groups; enzyme inhibitors
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.202001909

Controlling the activity of enzymes is an important feature for many processes in medicine, bioanalytics, and biotechnology. So far, it has not been possible to fully switch biocatalysts on and off by thermoresponsive enzyme inhibitors. Herein, we present poly(2‐oxazoline)s with iminodiacetic acid end groups (POx‐IDA) that are lower critical solution temperature (LCST) polymers and thus thermosensitive. They are capable of reversibly inhibiting the activity of horse radish peroxidase and laccase by more than 99 %. Increasing the temperature makes the POx‐IDA precipitate, which leads to 100 % recovery of the enzyme activity. This switching cycle is fully reversible. The LCST of the POx‐IDA can be tuned by varying the polymer composition to generate a wide range of switching windows.
Thermoresponsive co(poly‐2‐oxazoline)s with a 2,2′‐imino diacetate end group are capable of fully deactivating the enzymes laccase and horse radish peroxidase at different temperatures varying from 4–40 °C. Increasing the temperature results in full activity of both enzymes due to aggregation of the polymeric inhibitors. The process is fully reversible and does not interfere with the protein′s activity.